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Abd Rahman F, Azwa FN. Comparative Dental Pulp Stem Cells (DPSCs) and Periodontal Ligament Stem Cells (PDLSCs): Difference in effect of aspirin on osteoblast potential of PDLSCs and DPSCs. Tissue Cell 2025; 94:102776. [PMID: 40022908 DOI: 10.1016/j.tice.2025.102776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 01/27/2025] [Accepted: 02/01/2025] [Indexed: 03/04/2025]
Abstract
Periodontal Ligament Stem Cells (PDLSCs) and Dental Pulp Stem Cells (DPSCs) are mesenchymal stem cells with the ability to self-renew and differentiate into three lineages. One significant advantage of dental stem cells, such as PDLSCs and DPSCs, is their ease of harvest compared to other types of mesenchymal stem cells (MSCs). While MSCs are highly valued in bone tissue engineering, MSCs sourced from dental tissues, such as PDLSCs and DPSCs, offer promising options for periodontal regeneration because they are more easily accessible and can be collected through minimally invasive methods. Currently, PDLSCs and DPSCs exhibit a strong ability to undergo osteogenic differentiation when stimulated by factors such as growth factors, chemicals, and paracrine signaling. It has been shown that aspirin (ASA) can enhance the osteoblastic potential of PDLSCs and DPSCs, although the exact mechanism remains unclear. This article examines the origin and features of mesenchymal stem cells, the bone regeneration potential of DPSCs and PDLSCs, the factors that enhance their osteogenic differentiation, and a comparison of PDLSCs and DPSCs regarding their proliferation and differentiation abilities. Additionally, we will examine the effects of aspirin on PDLSCs and DPSCs. In conclusion, PDLSCs show a greater effect on osteoblast differentiation.
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Affiliation(s)
- Fazliny Abd Rahman
- School of Dentistry (SoD), Management & Science University (MSU), University Drive, Off Persiaran Olahraga, 40100 Shah Alam, Selangor.
| | - Fatin Nur Azwa
- Faculty of Dentistry, Oral Cancer Research Centre (ORCC), University of Malaya (UM), Wilayah Persekutuan, Kuala Lumpur 50603, Malaysia
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Boopathy K, Palaniyandi T, Ravi M, Wahab MRA, Baskar G, Rab SO, Saeed M, Balaramnavar VM. Exploring the potential of stem cell therapy: Applications, types, and future directions. Acta Histochem 2025; 127:152237. [PMID: 40020616 DOI: 10.1016/j.acthis.2025.152237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 02/14/2025] [Accepted: 02/18/2025] [Indexed: 03/03/2025]
Abstract
One of the most significant treatment approaches now accessible is stem cell therapy. Over the last few decades, a lot of study has been done in this field, and this fascinating feature of plasticity could have therapeutic uses. The potential of stem cells to restore function lost as a result of disease, trauma, congenital defects, and age has made stem cell research a key priority for scientific and medical organizations across the world. Stem cells are a crucial topic of study in regenerative medicine because of their capacity to replace, repair, or regenerate damaged cells, tissues, or organs. As a result, stem cell therapy is being used as a treatment strategy for a number of illnesses. Because stem cells may proliferate indefinitely and generate vast quantities of differentiated cells needed for transplantation, they hold enormous promise for regenerative medicine. Stem cells can be reprogrammed from adult cell types or originate from embryonic or fetal origins. Depending on their availability and place of origin, stem cells can be totipotent, pluripotent, multipotent, oligopotent, or unipotent. With stem cell treatment, many ailments, including diabetes, liver disease, infertility, wounds and traumas, neurological disorders, cardiovascular disease, and cancer, might be cured. Various types of stem cell treatment are described in this review along with their applications in different therapeutic fields, ethical considerations, and advantages and disadvantages.
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Affiliation(s)
- KeerthiShri Boopathy
- Department of Biotechnology, Dr. M.G.R Educational and Research Institute, Chennai 600095, India
| | - Thirunavukkarasu Palaniyandi
- Department of Biotechnology, Dr. M.G.R Educational and Research Institute, Chennai 600095, India; ACS-Advanced Medical Research Institute, Dr. M.G.R Educational and Research Institute, Chennai 600077, India.
| | - Maddaly Ravi
- Department of Human Genetics, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu 600 116, India
| | | | - Gomathy Baskar
- Department of Biotechnology, Dr. M.G.R Educational and Research Institute, Chennai 600095, India
| | - Safia Obaidur Rab
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Mohd Saeed
- Department of Biology, College of Science, University of Hail, Hail, Saudi Arabia
| | - Vishal M Balaramnavar
- School of Pharmacy and Research Centre, Sanskriti University, Chhata, Mathura, Uttar Pradesh 281401, India
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Ma L, Li M, Xuan G, Dai Y. METTL14-mediated m6A RNA methylation promotes the osteogenic differentiation of pPDLSCs by regulating WNT3A. Odontology 2025:10.1007/s10266-025-01097-2. [PMID: 40249476 DOI: 10.1007/s10266-025-01097-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 03/24/2025] [Indexed: 04/19/2025]
Abstract
Periodontitis is a chronic inflammatory disease that leads to the loss of periodontal supporting tissue. Furthermore, human periodontal ligament stem cells (hPDLSCs) are identified as candidate cells for the regeneration of periodontal and alveolar bone tissues. N6-Methyladenosine (m6A) performs a vital role in osteoporosis and bone metabolism. However, the role and mechanism of Methyltransferase-like 14 (METTL14) in the osteogenic differentiation of PDLSCs from periodontitis sufferers (pPDLSCs) is unclear. In this research, GSE223924 database analyzed the expression of METTL14 and Wnt Family Member 3A (WNT3A) in gingival tissue samples of 10 healthy subjects, 10 patients with periodontitis and peri-implantitis. RT-qPCR and western blot detected METTL14, COL1A1, Runx2, ALP, and WNT3A mRNA level and protein level. Osteogenic differentiation was evaluated by Alizarin Red S staining and ALP activity. MeRIP and dual-luciferase reporter assays verified interaction between METTL14 and WNT3A. GSE223924 database showed METTL14 was differentially expressed in patients with periodontitis and peri-implantitis. Furthermore, our data verified that METTL14 and WNT3A expression were decreased in pPDLSCs and were upregulated by osteogenic induction. METTL14 promoted osteogenic differentiation of pPDLSCs. METTL14 regulated WNT3A mRNA expression via m6A methylation. METTL14 facilitates osteogenic differentiation of pPDLSCs via modulating WNT3A, providing a possible target for improving alveolar bone regeneration outcomes.Highlights 1. METTL14 expression was decreased in pPDLSCs 2. METTL14 knockdown negatively regulated the osteogenic differentiation of pPDLSCs 3. WNT3A mRNA was a m6A-methylated target by METTL14.
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Affiliation(s)
- Lan Ma
- Department of Stomatology, Shaoxing People's Hospital, Zhongxing North Road NO.568, Shaoxing, 312000, China
| | - Min Li
- Department of Stomatology, Shaoxing People's Hospital, Zhongxing North Road NO.568, Shaoxing, 312000, China
| | - Guihong Xuan
- Department of Stomatology, Shaoxing People's Hospital, Zhongxing North Road NO.568, Shaoxing, 312000, China
| | - Ying Dai
- Department of Stomatology, Shaoxing People's Hospital, Zhongxing North Road NO.568, Shaoxing, 312000, China.
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Prucksakorn T, Mutirangura A, Pavasant P, Subbalekha K. Altered Methylation Levels in LINE-1 in Dental Pulp Stem Cell-Derived Osteoblasts. Int Dent J 2025; 75:1269-1276. [PMID: 39368926 PMCID: PMC11976608 DOI: 10.1016/j.identj.2024.09.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 08/20/2024] [Accepted: 09/05/2024] [Indexed: 10/07/2024] Open
Abstract
OBJECTIVES Long interspersed nuclear element-1 (LINE-1) and Alu elements are major targets of methylation, an epigenetic mechanism that is associated with several biological processes. Alterations of methylation of LINE-1 and Alu have been reported in cancers, diseases, and ageing. However, these alterations have not been studied in osteogenic differentiation of dental pulp stem cells (DPSCs), which are a promising source of tissue regeneration. METHOD This study was performed to investigate the methylation level of LINE-1 and Alu in dental pulp stem cell-derived osteoblasts (DPSC-DOs). By using the combined bisulfite restriction analysis, the levels of total methylation and 4 patterns of methylated cytosine-phosphate-guanine (CpG) dinucleotides of LINE-1 and Alu were compared between DPSC-DOs and DPSCs. RESULT The levels of total methylation and hypermethylated CpG dinucleotides of LINE-1 were significantly lower (P = .015 and .021, respectively), whilst levels of one pattern of partial methylated CpG dinucleotides were significantly higher in DPSC-DOs than DPSCs (P = .021). The methylation of Alu was not significantly different between DPSCs and DPSC-DOs. CONCLUSIONS Methylation alterations of LINE-1 but not Alu were found in osteogenic differentiation of DPSCs. The results of this study offer foundational insights into osteoblast differentiation from an epigenetic perspective and may contribute to advancements in bone regeneration therapy in the future.
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Affiliation(s)
- Thitapat Prucksakorn
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Apiwat Mutirangura
- Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculyzety of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Prasit Pavasant
- Mineralized Tissue Research Unit, Department of Anatomy, Chulalongkorn University, Bangkok, Thailand
| | - Keskanya Subbalekha
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
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Carvalho TO, de Almeida WP, Palma FR, Pilati PVF, Zanardo V, Chaves AJL, Pilati SFM. Effect of ozone and low power laser as therapeutic alternatives on the alveolar repair process after tooth extraction in rats wistar exposed to nicotine. Oral Maxillofac Surg 2025; 29:54. [PMID: 39918660 DOI: 10.1007/s10006-025-01339-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 01/14/2025] [Indexed: 02/09/2025]
Abstract
PURPOSE The aim of this study was to evaluate the alveolar repair process in rats exposed to nicotine after tooth extraction, using ozonised water and low-power laser therapy (LPLT) as therapeutic adjuvants. MATERIALS AND METHODS Thirty wistar rats (Rattus Norvegicus) were used and given the nicotine solution via subcutaneous tissue. After 7 days, the upper right central incisor was surgically extracted. Three days after the surgical procedure, the animals continued to receive nicotine until the day of euthanasia, totalling 21 days after extraction. RESULTS The result was that the groups that received coadjuvant therapy had neoformed mature bone, unlike the group that did not receive it. CONCLUSIONS Based on the literature and the results obtained, we can conclude that nicotine negatively influenced the healing process and bone repair in the alveoli; however, the use of ozonised water and LPLT, even in the presence of nicotine, was effective, as it enhanced the repair process, making them good options for surgical procedures in patients who smoke.
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Affiliation(s)
- Thainy Oliveira Carvalho
- University of Vale Do Itajaí (UNIVALI), R. Uruguai, 458, C5 - Centro, Itajaí - SC, 88302-901, Brazil
| | - Wilson Pereira de Almeida
- University of Vale Do Itajaí (UNIVALI), R. Uruguai, 458, C5 - Centro, Itajaí - SC, 88302-901, Brazil
| | - Fabiano Rodrigues Palma
- Anaesthesiology and Surgery, Universidade Do Vale Do Itajaí (UNIVALI), R. Uruguai, 458, C5 - Centro, Itajaí - SC, 88302-901, Brazil
| | | | - Victoria Zanardo
- University of Vale Do Itajaí (UNIVALI), R. Uruguai, 458, C5 - Centro, Itajaí - SC, 88302-901, Brazil
| | - Anna Júlia Leduc Chaves
- University of Vale Do Itajaí (UNIVALI), R. Uruguai, 458, C5 - Centro, Itajaí - SC, 88302-901, Brazil
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Zhao T, Zhong Q, Sun Z, Yu X, Sun T, An Z. Decoding SFRP2 progenitors in sustaining tooth growth at single-cell resolution. Stem Cell Res Ther 2025; 16:58. [PMID: 39920788 PMCID: PMC11806734 DOI: 10.1186/s13287-025-04190-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 01/24/2025] [Indexed: 02/09/2025] Open
Abstract
BACKGROUND Single-cell transcriptomics has revolutionized tooth biology by uncovering previously unexplored areas. The mouse is a widely used model for studying human tissues and diseases, including dental pulp tissues. While human and mouse molars share many similarities, mouse incisors differ significantly from human teeth due to their continuous growth throughout their lifespan. The application of findings from mouse teeth to human disease remains insufficiently explored. METHODS Leveraging multiple single-cell datasets, we constructed a comprehensive dental pulp cell landscape to delineate tissue similarities and species-specific differences between humans and mice. RESULTS We identified a distinct cell population, Sfrp2hi fibroblast progenitors, found exclusively in mouse incisors and the developing tooth root of human molars. These cells play a crucial role in sustaining continuous tissue growth. Mechanistically, we found that the transcription factor Twist1, regulated via MAPK phosphorylation, binds to the Sfrp2 promoter and modulates Wnt signaling activation to maintain stem cell identity. CONCLUSIONS Our study reveals a previously unrecognized subset of dental mesenchymal stem cells critical for tooth growth. This distinct subset, evolutionarily conserved between humans and mice, provides valuable insights into translational approaches for dental tissue regeneration and repair.
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Affiliation(s)
- Tianyuan Zhao
- Department of Oral Biology, School and Hospital of Stomatology, Jilin University, Changchun, China
- Key Laboratory of Tooth Development and Bone Remodeling of Jilin Province, School and Hospital of Stomatology, Jilin University, Changchun, China
| | - Qing Zhong
- Department of Oral Biology, School and Hospital of Stomatology, Jilin University, Changchun, China
- Key Laboratory of Tooth Development and Bone Remodeling of Jilin Province, School and Hospital of Stomatology, Jilin University, Changchun, China
| | - Zewen Sun
- Department of Oral Biology, School and Hospital of Stomatology, Jilin University, Changchun, China
- Key Laboratory of Tooth Development and Bone Remodeling of Jilin Province, School and Hospital of Stomatology, Jilin University, Changchun, China
| | - Xiaoyi Yu
- Department of Oral Biology, School and Hospital of Stomatology, Jilin University, Changchun, China
- Key Laboratory of Tooth Development and Bone Remodeling of Jilin Province, School and Hospital of Stomatology, Jilin University, Changchun, China
| | - Tianmeng Sun
- Department of Oral Biology, School and Hospital of Stomatology, Jilin University, Changchun, China
- Key Laboratory of Tooth Development and Bone Remodeling of Jilin Province, School and Hospital of Stomatology, Jilin University, Changchun, China
| | - Zhengwen An
- Department of Oral Biology, School and Hospital of Stomatology, Jilin University, Changchun, China.
- Key Laboratory of Tooth Development and Bone Remodeling of Jilin Province, School and Hospital of Stomatology, Jilin University, Changchun, China.
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Alizadeh SD, Hassan Zadeh Tabatabaei MS, Rezaei Zadeh Rukerd M, Tabrizi R, Masoomi R, Banihashemian SZ, Pourmasjedi SS, Ghodsi Z, Pour-Rashidi A, Harrop J, Rahimi-Movaghar V. The safety and efficacy of stem cell therapy for diabetic peripheral neuropathy in animal studies: A systematic review and meta-analysis. Neuroscience 2025; 566:49-59. [PMID: 39706518 DOI: 10.1016/j.neuroscience.2024.12.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 12/14/2024] [Accepted: 12/17/2024] [Indexed: 12/23/2024]
Abstract
Diabetic peripheral neuropathy (DPN) is the most common form of diabetic neuropathy, representing 75% of cases and posing a substantial public health challenge. Emerging evidence from animal studies indicates that stem cell therapy holds significant promise as a potential treatment for diabetic neuropathy. Nevertheless, a comprehensive evaluation of the safety and efficacy of stem cell therapy for DPN in animal studies remains outstanding. A systematic search of MEDLINE, Embase, Scopus, the Web of Science, and the CENTRAL was performed. The time period was up to January 31, 2024. All animal studies investigating the stem cell therapy for treating DPN were included. A random-effects model to combine effect sizes in our meta-analysis was applied. 29 out of the 5431 records met the eligibility criteria. In these studies, stem cell therapy improved motor and sensory nerve conduction velocity, compound muscle action potential (CMAP), and sciatic nerve blood flow. Post-treatment, mechanical and thermal nociceptive thresholds decreased. Rats had significant improvement in axonal circularity, nerve growth factor, and transforming growth factor beta 1; mice had significant increase in weight, CMAP, and angiopoietin 1. The stem cell subgroup analysis showed that dental pulp stem cells had the greatest effects across all parameters, while bone marrow mononuclear cells had strong biochemical responses. Stem cell therapy demonstrates promising efficacy in ameliorating neuropathic symptoms in DPN animal models. Human patient studies and targeted treatment procedures for specific neuropathic disorders are advocated to improve therapeutic outcomes.
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Affiliation(s)
- Seyed Danial Alizadeh
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mohammad Rezaei Zadeh Rukerd
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Reza Tabrizi
- Noncommunicable Diseases Research Center, Fasa University of Medical Science, Fasa, Iran
| | - Rasoul Masoomi
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | | | - Zahra Ghodsi
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Pour-Rashidi
- Department of Neurosurgery, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran; Founder of Neurosurgical Research Network, Universal Scientific Education and Research Network, Tehran, Iran
| | - James Harrop
- Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Vafa Rahimi-Movaghar
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran; Universal Scientific Education and Research Network, Tehran, Iran.
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Gallo MC, Elias A, Reynolds J, Ball JR, Lieberman JR. Regional Gene Therapy for Bone Tissue Engineering: A Current Concepts Review. Bioengineering (Basel) 2025; 12:120. [PMID: 40001640 PMCID: PMC11852166 DOI: 10.3390/bioengineering12020120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 01/20/2025] [Accepted: 01/24/2025] [Indexed: 02/27/2025] Open
Abstract
The management of segmental bone defects presents a complex reconstruction challenge for orthopedic surgeons. Current treatment options are limited by efficacy across the spectrum of injury, morbidity, and cost. Regional gene therapy is a promising tissue engineering strategy for bone repair, as it allows for local implantation of nucleic acids or genetically modified cells to direct specific protein expression. In cell-based gene therapy approaches, a variety of different cell types have been described including mesenchymal stem cells (MSCs) derived from multiple sources-bone marrow, adipose, skeletal muscle, and umbilical cord tissue, among others. MSCs, in particular, have been well studied, as they serve as a source of osteoprogenitor cells in addition to providing a vehicle for transgene delivery. Furthermore, MSCs possess immunomodulatory properties, which may support the development of an allogeneic "off-the-shelf" gene therapy product. Identifying an optimal cell type is paramount to the successful clinical translation of cell-based gene therapy approaches. Here, we review current strategies for the management of segmental bone loss in orthopedic surgery, including bone grafting, bone graft substitutes, and operative techniques. We also highlight regional gene therapy as a tissue engineering strategy for bone repair, with a focus on cell types and cell sources suitable for this application.
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Affiliation(s)
- Matthew C. Gallo
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA; (M.C.G.); (A.E.); (J.R.); (J.R.B.)
| | - Aura Elias
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA; (M.C.G.); (A.E.); (J.R.); (J.R.B.)
| | - Julius Reynolds
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA; (M.C.G.); (A.E.); (J.R.); (J.R.B.)
| | - Jacob R. Ball
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA; (M.C.G.); (A.E.); (J.R.); (J.R.B.)
| | - Jay R. Lieberman
- Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA; (M.C.G.); (A.E.); (J.R.); (J.R.B.)
- Alfred E. Mann Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA
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Cheng X, Huang L, Wang H, Lei S, Chan C, Yang X, Huang Y. The combination of odontogenic stem cells and mandibular advancement promotes the length of the mandible in adult rats by facilitating the development of condylar cartilage. Stem Cell Res Ther 2024; 15:441. [PMID: 39563452 DOI: 10.1186/s13287-024-04055-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 11/07/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND Mandibular retraction is a prevalent dental and maxillofacial deformity that negatively affects patients' functional health and facial aesthetics. It has been challenging to achieve optimal outcomes for patients who have passed the peak of growth and development using only functional orthopedic treatment. There is a pressing need to explore innovative methods to promote the adaptive remodeling of adult condylar cartilage and the mandible in response to external stimuli. This study aimed to investigate the impact of varying injection frequencies of stem cells from the apical papilla (SCAPs) on the growth and development of condylar cartilage and the mandible, as well as their potential for adaptive remodeling. METHODS The study was conducted on 8-week-old adult male Sprague-Dawley rats. The effects of SCAPs injection and different durations of mandibular advancement (MA) on the adaptive remodeling of condylar cartilage and the mandible were assessed. After the initial experimental findings, various injection frequencies of SCAPs were applied to determine the most effective conditions for promoting the growth and adaptive remodeling of condylar cartilage and the mandible during an 8-week period of mandibular advancement. RESULTS The study found that rats with extended mandibular lead times (8 weeks) or an appropriately increased frequency of mandibular leading time (once every 2 weeks or once every 1 week) exhibited increased lengths of the mandibular body and ascending branch, and a thickened full layer of condylar cartilage. The highest proportions of the proliferative layer, mature layer, and hypertrophic layer were observed in these rats. Additionally, there was a significant increase in the expression levels of SOX9 and COL2A1. CONCLUSION The data from this study suggest that adult rats, even after missing their peak growth period, retain the potential for continued growth and development of their condylar cartilage. By prolonging the duration of mandibular advancement and administering injections of stem cells from the apical papilla (SCAPs), it is possible to stimulate the growth and development of the mandibular condyle.
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Affiliation(s)
- Xin Cheng
- School of Stomatology, Jinan University, Guangzhou, 510632, China
| | - Liangching Huang
- School of Stomatology, Jinan University, Guangzhou, 510632, China
| | - Huijuan Wang
- School of Stomatology, Jinan University, Guangzhou, 510632, China
| | - SiLong Lei
- School of Stomatology, Jinan University, Guangzhou, 510632, China
| | - Chichong Chan
- School of Stomatology, Jinan University, Guangzhou, 510632, China
| | - Xuesong Yang
- Division of Histology and Embryology, Medical College, Jinan University, Guangzhou, 510632, China.
- International School, Guangzhou Huali College, Zengcheng, Guangzhou, 511325, China.
| | - Yue Huang
- School of Stomatology, Jinan University, Guangzhou, 510632, China.
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10
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Rostami M, Farahani P, Esmaelian S, Bahman Z, Fadel Hussein A, A Alrikabi H, Hosseini Hooshiar M, Yasamineh S. The Role of Dental-derived Stem Cell-based Therapy and Their Derived Extracellular Vesicles in Post-COVID-19 Syndrome-induced Tissue Damage. Stem Cell Rev Rep 2024; 20:2062-2103. [PMID: 39150646 DOI: 10.1007/s12015-024-10770-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/02/2024] [Indexed: 08/17/2024]
Abstract
Long coronavirus disease 2019 (COVID-19) is linked to an increased risk of post-acute sequelae affecting the pulmonary and extrapulmonary organ systems. Up to 20% of COVID-19 patients may proceed to a more serious form, such as severe pneumonia, acute respiratory distress syndrome (ARDS), or pulmonary fibrosis. Still, the majority of patients may only have mild, self-limiting sickness. Of particular concern is the possibility of parenchymal fibrosis and lung dysfunction in long-term COVID-19 patients. Furthermore, it has been observed that up to 43% of individuals hospitalized with COVID-19 also had acute renal injury (AKI). Care for kidney, brain, lung, cardiovascular, liver, ocular, and tissue injuries should be included in post-acute COVID-19 treatment. As a powerful immunomodulatory tool in regenerative medicine, dental stem cells (DSCs) have drawn much interest. Numerous immune cells and cytokines are involved in the excessive inflammatory response, which also has a significant effect on tissue regeneration. A unique reservoir of stem cells (SCs) for treating acute lung injury (ALI), liver damage, neurological diseases, cardiovascular issues, and renal damage may be found in tooth tissue, according to much research. Moreover, a growing corpus of in vivo research is connecting DSC-derived extracellular vesicles (DSC-EVs), which are essential paracrine effectors, to the beneficial effects of DSCs. DSC-EVs, which contain bioactive components and therapeutic potential in certain disorders, have been shown as potentially effective therapies for tissue damage after COVID-19. Consequently, we explore the properties of DSCs in this work. Next, we'll look at how SARS-CoV-2 affects tissue damage. Lastly, we have looked at the use of DSCs and DSC-EVs in managing COVID-19 and chronic tissue damage, such as injury to the heart, brain, lung, and other tissues.
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Affiliation(s)
- Mitra Rostami
- School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
| | - Pouria Farahani
- Doctor of Dental Surgery, Faculty of Dentistry, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Samar Esmaelian
- Faculty of Dentistry, Islamic Azad University, Tehran Branch, Tehran, Iran
| | - Zahra Bahman
- Faculty of dentistry, Belarusian state medical university, Minsk, Belarus
| | | | - Hareth A Alrikabi
- Collage of Dentist, National University of Science and Technology, Dhi Qar, 64001, Iraq
| | | | - Saman Yasamineh
- Young Researchers and Elite Club, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
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Zhao JZ, Ge YY, Xue LF, Xu YX, Yue J, Li C, Xiao WL. CA1 Modulates the Osteogenic Differentiation of Dental Follicle Stem Cells by Activating the BMP Signaling Pathway In Vitro. Tissue Eng Regen Med 2024; 21:855-865. [PMID: 38652220 PMCID: PMC11286914 DOI: 10.1007/s13770-024-00642-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 03/09/2024] [Accepted: 03/21/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND Carbonic anhydrase 1 (CA1) has been found to be involved in osteogenesis and osteoclast in various human diseases, but the molecular mechanisms are not completely understood. In this study, we aim to use siRNA and lentivirus to reduce or increase the expression of CA1 in Dental follicle stem cells (DFSCs), in order to further elucidate the role and mechanism of CA1 in osteogenesis, and provide better osteogenic growth factors and stem cell selection for the application of bone tissue engineering in alveolar bone fracture transplantation. METHODS The study used RNA interference and lentiviral vectors to manipulate the expression of the CA1 gene in DFSCs during in vitro osteogenic induction. The expression of osteogenic marker genes was evaluated and changes in CA1, alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and Bone morphogenetic proteins (BMP2) were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). The osteogenic effect was assessed through Alizarin Red staining. RESULTS The mRNA and protein expression levels of CA1, ALP, RUNX2, and BMP2 decreased distinctly in the si-CA1 group than other groups (p < 0.05). In the Lentivirus-CA1 (LV-CA1) group, the mRNA and protein expressions of CA1, ALP, RUNX2, and BMP2 were amplified to varying degrees than other groups (p < 0.05). Apart from CA1, BMP2 (43.01%) and ALP (36.69%) showed significant upregulation (p < 0.05). Alizarin red staining indicated that the LV-CA1 group produced more calcified nodules than other groups, with a higher optical density (p < 0.05), and the osteogenic effect was superior. CONCLUSIONS CA1 can impact osteogenic differentiation via BMP related signaling pathways, positioning itself upstream in osteogenic signaling pathways, and closely linked to osteoblast calcification and ossification processes.
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Affiliation(s)
- Jin-Ze Zhao
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- School of Stomatology, Qingdao University, Qingdao, 266023, China
| | - Ying-Ying Ge
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- School of Stomatology, Qingdao University, Qingdao, 266023, China
| | - Ling-Fa Xue
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- School of Stomatology, Qingdao University, Qingdao, 266023, China
| | - Yao-Xiang Xu
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- School of Stomatology, Qingdao University, Qingdao, 266023, China
| | - Jin Yue
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- School of Stomatology, Qingdao University, Qingdao, 266023, China
| | - Cong Li
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- School of Stomatology, Qingdao University, Qingdao, 266023, China
| | - Wen-Lin Xiao
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
- School of Stomatology, Qingdao University, Qingdao, 266023, China.
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Kuang YH, Zhu W, Lin G, Cheng LM, Qin Q, Huang ZJ, Shi YL, Zhang CL, Xu JH, Yan KX, Lv CZ, Li W, Han Q, Stambler I, Lim LW, Chakrabarti S, Ulfhake B, Min KJ, Ellison-Hughes G, Cho WC, Jin K, Yao D, Lu C, Zhao RC, Chen X. Expert Consensus on the Application of Stem Cells in Psoriasis Research and Clinical Trials. Aging Dis 2024:AD.2024.0012. [PMID: 39012666 DOI: 10.14336/ad.2024.0012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 06/04/2024] [Indexed: 07/17/2024] Open
Abstract
Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.
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Affiliation(s)
- Ye-Hong Kuang
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- China Dermatologist Association, China
- Chinese Society of Dermatology, China
| | - Wu Zhu
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- China Dermatologist Association, China
- Chinese Society of Dermatology, China
| | - Ge Lin
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China
- National Engineering Research Center of Human Stem Cell, Changsha, China
| | - La-Mei Cheng
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China
- National Engineering Research Center of Human Stem Cell, Changsha, China
| | - Qun Qin
- The Office of Drug Clinical Trials Institution, Xiangya Hospital, Central South University, Changsha, China
| | - Zhi-Jun Huang
- Center for Clinical Pharmacology, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Yu-Ling Shi
- China Dermatologist Association, China
- Chinese Society of Dermatology, China
- Department of Dermatology, Shanghai Skin Disease Hospital, Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China
| | - Chun-Lei Zhang
- China Dermatologist Association, China
- Chinese Society of Dermatology, China
- Department of Dermatology, Peking University Third Hospital, Beijing, China
| | - Jin-Hua Xu
- China Dermatologist Association, China
- Chinese Society of Dermatology, China
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Ke-Xiang Yan
- China Dermatologist Association, China
- Chinese Society of Dermatology, China
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Cheng-Zhi Lv
- China Dermatologist Association, China
- Chinese Society of Dermatology, China
- Department of Dermatology, Dalian Dermatosis Hospital, Dalian, China
| | - Wei Li
- Department of Dermatology, Rare Diseases Center, West China Hospital, Sichuan University, Chengdu, China
- China Dermatologist Association, China
- Chinese Society of Dermatology, China
| | - Qin Han
- International Society on Aging and Disease, Fort Worth, TX, USA
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
- Center for Excellence in Tissue Engineering, Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381), Beijing, China
| | - Ilia Stambler
- International Society on Aging and Disease, Fort Worth, TX, USA
- Department of Science, Technology and Society, Bar Ilan University, Ramat Gan, Israel
| | - Lee Wei Lim
- International Society on Aging and Disease, Fort Worth, TX, USA
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Sasanka Chakrabarti
- International Society on Aging and Disease, Fort Worth, TX, USA
- Maharishi Markandeshwar Deemed University, Mullana-Ambala, India
| | - Brun Ulfhake
- International Society on Aging and Disease, Fort Worth, TX, USA
- Karolinska University Hospital, Stockholm, Sweden
| | - Kyung-Jin Min
- International Society on Aging and Disease, Fort Worth, TX, USA
- Department of Biological Sciences, Inha University, Incheon, Republic of Korea
| | - Georgina Ellison-Hughes
- International Society on Aging and Disease, Fort Worth, TX, USA
- School of Basic and Medical Biosciences, Faculty of Life Sciences &;amp Medicine, King's College London, London, UK
| | - William C Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China
| | - Kunlin Jin
- International Society on Aging and Disease, Fort Worth, TX, USA
- University of North Texas Health Science Center, Bryan, TX, USA
| | - Danni Yao
- Department of Dermatology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Chuanjian Lu
- Department of Dermatology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Robert Chunhua Zhao
- International Society on Aging and Disease, Fort Worth, TX, USA
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
- Center for Excellence in Tissue Engineering, Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381), Beijing, China
| | - Xiang Chen
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
- China Dermatologist Association, China
- Chinese Society of Dermatology, China
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Ma M. Role of Hypoxia in Mesenchymal Stem Cells from Dental Pulp: Influence, Mechanism and Application. Cell Biochem Biophys 2024; 82:535-547. [PMID: 38713403 PMCID: PMC11344735 DOI: 10.1007/s12013-024-01274-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2024] [Indexed: 05/08/2024]
Abstract
Mesenchymal stem cells (MSCs) from dental pulp (DP-MSCs), which include dental pulp stem cells (DPSCs) isolated from permanent teeth and stem cells from human exfoliated deciduous teeth (SHED), have emerged as highly promising cell sources for tissue regeneration, due to their high proliferative rate, multi-lineage differentiation capability and non-invasive accessibility. DP-MSCs also exert extensive paracrine effects through the release of extracellular vesicles (EVs) and multiple trophic factors. To be noted, the microenvironment, commonly referred to as the stem cell niche, plays a crucial role in shaping the functionality and therapeutic effects of DP-MSCs, within which hypoxia has garnered considerable attention. Extensive research has demonstrated that hypoxic conditions profoundly impact DP-MSCs. Specifically, hypoxia promotes DP-MSC proliferation, survival, stemness, migration, and pro-angiogenic potential while modulating their multi-lineage differentiation capacity. Furthermore, hypoxia stimulates the paracrine activities of DP-MSCs, leading to an increased production of EVs and soluble factors. Considering these findings, hypoxia preconditioning has emerged as a promising approach to enhance the therapeutic potential of DP-MSCs. In this comprehensive review, we provide a systematic overview of the influence of hypoxia on DP-MSCs, shedding light on the underlying mechanisms involved. Moreover, we also discuss the potential applications of hypoxia-preconditioned DP-MSCs or their secretome in tissue regeneration. Additionally, we delve into the methodologies employed to simulate hypoxic environments. This review aims to promote a comprehensive and systematic understanding of the hypoxia-induced effects on DP-MSCs and facilitate the refinement of regenerative therapeutic strategies based on DP-MSCs.
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Affiliation(s)
- Muyuan Ma
- School of Medicine, South China University of Technology, Guangzhou, China.
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14
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Huang L, Chen X, Yang X, Zhang Y, Liang Y, Qiu X. Elucidating epigenetic mechanisms governing odontogenic differentiation in dental pulp stem cells: an in-depth exploration. Front Cell Dev Biol 2024; 12:1394582. [PMID: 38863943 PMCID: PMC11165363 DOI: 10.3389/fcell.2024.1394582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 05/13/2024] [Indexed: 06/13/2024] Open
Abstract
Epigenetics refers to the mechanisms such as DNA methylation and histone modification that influence gene expression without altering the DNA sequence. These epigenetic modifications can regulate gene transcription, splicing, and stability, thereby impacting cell differentiation, development, and disease occurrence. The formation of dentin is intrinsically linked to the odontogenic differentiation of dental pulp stem cells (DPSCs), which are recognized as the optimal cell source for dentin-pulp regeneration due to their varied odontogenic potential, strong proliferative and angiogenic characteristics, and ready accessibility Numerous studies have demonstrated the critical role of epigenetic regulation in DPSCs differentiation into specific cell types. This review thus provides a comprehensive review of the mechanisms by which epigenetic regulation controls the odontogenesis fate of DPSCs.
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Affiliation(s)
| | | | | | | | | | - Xiaoling Qiu
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China
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15
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Xu S, Zhao L, Li Y, Gu X, Liu Z, Han X, Li W, Ma W. Activating the healing process: three-dimensional culture of stem cells in Matrigel for tissue repair. BMC Biotechnol 2024; 24:36. [PMID: 38796454 PMCID: PMC11128131 DOI: 10.1186/s12896-024-00862-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 05/22/2024] [Indexed: 05/28/2024] Open
Abstract
BACKGROUND To establish a strategy for stem cell-related tissue regeneration therapy, human gingival mesenchymal stem cells (hGMSCs) were loaded with three-dimensional (3D) bioengineered Matrigel matrix scaffolds in high-cell density microtissues to promote local tissue restoration. METHODS The biological performance and stemness of hGMSCs under 3D culture conditions were investigated by viability and multidirectional differentiation analyses. A Sprague‒Dawley (SD) rat full-thickness buccal mucosa wound model was established, and hGMSCs/Matrigel were injected into the submucosa of the wound. Autologous stem cell proliferation and wound repair in local tissue were assessed by histomorphometry and immunohistochemical staining. RESULTS Three-dimensional suspension culture can provide a more natural environment for extensions and contacts between hGMSCs, and the viability and adipogenic differentiation capacity of hGMSCs were significantly enhanced. An animal study showed that hGMSCs/Matrigel significantly accelerated soft tissue repair by promoting autologous stem cell proliferation and enhancing the generation of collagen fibers in local tissue. CONCLUSION Three-dimensional cell culture with hydrogel scaffolds, such as Matrigel, can effectively improve the biological function and maintain the stemness of stem cells. The therapeutic efficacy of hGMSCs/Matrigel was confirmed, as these cells could effectively stimulate soft tissue repair to promote the healing process by activating the host microenvironment and autologous stem cells.
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Affiliation(s)
- Shukui Xu
- Department of Orthodontics, Hebei Key Laboratory of Stomatology, Hebei Clinical Research Center for Oral Diseases, School and Hospital of Stomatology, Hebei Medical University, Shijiahzuang, 050017, China
| | - Liru Zhao
- Department of Orthodontics, Hebei Key Laboratory of Stomatology, Hebei Clinical Research Center for Oral Diseases, School and Hospital of Stomatology, Hebei Medical University, Shijiahzuang, 050017, China
| | - Yinghui Li
- Department of Orthodontics, Hebei Key Laboratory of Stomatology, Hebei Clinical Research Center for Oral Diseases, School and Hospital of Stomatology, Hebei Medical University, Shijiahzuang, 050017, China
| | - Xiuge Gu
- Department of Orthodontics, Hebei Key Laboratory of Stomatology, Hebei Clinical Research Center for Oral Diseases, School and Hospital of Stomatology, Hebei Medical University, Shijiahzuang, 050017, China
| | - Ziyang Liu
- Department of Orthodontics, Hebei Key Laboratory of Stomatology, Hebei Clinical Research Center for Oral Diseases, School and Hospital of Stomatology, Hebei Medical University, Shijiahzuang, 050017, China
| | - Xing Han
- Department of Orthodontics, Hebei Key Laboratory of Stomatology, Hebei Clinical Research Center for Oral Diseases, School and Hospital of Stomatology, Hebei Medical University, Shijiahzuang, 050017, China
| | - Wenwen Li
- Department of Orthodontics, Hebei Key Laboratory of Stomatology, Hebei Clinical Research Center for Oral Diseases, School and Hospital of Stomatology, Hebei Medical University, Shijiahzuang, 050017, China
| | - Wensheng Ma
- Department of Orthodontics, School of Medicine, Tianjin Stomatological Hospital, Nankai University, Tianjin, 300041, China.
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, China.
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Karkehabadi H, Rahmati A, Abbaspourrokni H, Farmany A, Najafi R, Behroozi R, Rezaei-Soufi L, Abbasi R. Effect of magnesium oxide nanoparticles and LED irradiation on the viability and differentiation of human stem cells of the apical papilla. Biotechnol Lett 2024; 46:263-278. [PMID: 38326543 DOI: 10.1007/s10529-024-03471-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 12/15/2023] [Accepted: 01/26/2024] [Indexed: 02/09/2024]
Abstract
PURPOSE Currently, regenerative endodontic treatments are gaining more and more attention, and stem cells play a significant role in these treatments. In order to enhance stem cell proliferation and differentiation, a variety of methods and materials have been used. The purpose of this study was to determine the effects of magnesium oxide nanoparticles and LED irradiation on the survival and differentiation of human stem cells from apical papilla. METHODS The MTT test was used to measure the cell survival of SCAPs that had been exposed to different concentrations of magnesium oxide nanoparticles after 24 and 48 h, and the concentration with the highest cell survival rate was picked for further studies. The cells were classified into four distinct groups based on their treatment: (1) control, which received no exposure, (2) exposure to magnesium oxide nanoparticles, (3) exposure to light emitting diode (LED) irradiation (635 nm, 200 mW/cm2) for 30 s, (4) exposure simultaneously with magnesium oxide nanoparticles and LED irradiation. A green approach was employed to synthesize magnesium oxide nanoparticles. Quantitative real time PCR was used to measure the gene expression of osteo/odontogenic markers such as BSP, DSPP, ALP and DMP1 in all four groups after treatment, and Alizarin red S staining (ARS) was used to determine the osteogenic differentiation of SCAPs by demonstrating the Matrix mineralization. RESULTS The highest viability of SCAPs was observed after 24 h in concentration 1 and 10 µg/mL and after 48 h in concentration 1 µg/mL, which were not significantly different from the control group. In both times, the survival of SCAPs decreased with increasing concentration of magnesium oxide nanoparticles (MgONPs). According to the results of Real-time PCR, after 24 and 48 h, the highest differentiation of BSP, DMP1, ALP and DSPP genes was observed in the LED + MgONPs group, followed by MgONPs and then LED, and in all 3 experimental groups, it was significantly higher than control group (P < 0.05). Also, after 24 and 48 h, the density of ARS increased in all groups compared to the control group, and the highest density was observed in the MgONPs + LED and MgONPs groups. CONCLUSION This research concluded that exposure to SCAPs, MgONPs, and LED irradiation has a significant effect on enhancing gene expression of odontogenic/osteogenic markers and increasing matrix mineralization.
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Affiliation(s)
- Hamed Karkehabadi
- Department of Endodontics, Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Afsaneh Rahmati
- Department of Endodontics, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Hadiseh Abbaspourrokni
- Department of Endodontics, Faculty of Dentistry, Mazandaran University of Medical Sciences, Sari, Iran
| | - Abbas Farmany
- Dental Research Center, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Rezvan Najafi
- Department of Medical Molecular and Genetics, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | | | - Loghman Rezaei-Soufi
- Department of Operative Dentistry, Dental Research Center, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Roshanak Abbasi
- Department of Endodontics, Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
- Department of Endodontics, School of Dentistry, Lorestan University of Medical Sciences, Khorramabad, Iran.
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Abo El-Dahab MM, El Deen GN, Aly RM, Gheith M. Infrared diode laser enhances human periodontal ligament stem cells behaviour on titanium dental implants. Sci Rep 2024; 14:4155. [PMID: 38378776 PMCID: PMC10879096 DOI: 10.1038/s41598-024-54585-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 02/14/2024] [Indexed: 02/22/2024] Open
Abstract
Low level laser treatment (LLLT) is known for its photobiostimulatory and photobiomodulatory characteristics, which stimulate cell proliferation, increase cellular metabolism, and improve cellular regeneration. The objective of the present research was to assess the possible influence of infrared diode laser irradiation on the behaviour, attachment, and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) seeded on different types of dental implants. Two distinct types of implants, one subjected to laser surface treatment and the other treated with acid etching, were longitudinally divided into two halves and submerged in six wells culture plates. Both implants were subjected to infrared diode laser treatment, and subsequently, the morphology and attachment of cells were examined using scanning electron microscopy (SEM) after 14 and 21 days. The behaviour of (hPDLSCs) towards two types of implants, when exposed to osteogenic medium and low-level laser therapy (LLLT), was assessed using quantitative real-time polymerase chain reaction to measure the expression of stemness markers and osteogenic markers. The scanning electron microscopy (SEM) demonstrated that the application of infrared diode laser irradiation substantially improved the attachment of cells to both types of implants. The stemness gene markers were significantly down regulated in cells seeded on both surfaces when challenged with osteogenic media in relation to control. At 14 days, early osteogenic markers, were upregulated, while late osteogenic markers, were downregulated in both challenged groups. At the 21-day mark, hPDLSCs seeded on an acid-etched implant exhibited increased expression of all osteogenic markers in response to stimulation with osteogenic media and infra-red diode laser, in contrast to hPDLSCs seeded on a laser surface treated implant under the same conditions. Finally, the findings of our research revealed that when subjected to infrared diode laser, human periodontal ligament stem cells cultured on both types of implants demonstrated improved cellular attachment and differentiation. This suggested that infrared diode laser enhanced the activity of the cells surrounding the implants. Hence, the use of infrared diode laser could be pivotal in improving and expediting the clinical osseointegration process around dental implants.
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Affiliation(s)
- Mohamed M Abo El-Dahab
- Department of Basic Dental Science, Oral and Dental Research Institute, National Research Centre, 33 El Buhouth St., Dokki, Cairo, 12622, Egypt
- Stem Cell Laboratory, Center of Excellence for Advanced Sciences, National Research Centre, Cairo, Egypt
| | - Ghada Nour El Deen
- Molecular Genetics and Enzymology Department, Human Genetic and Genome Research Institute, National Research Centre, Dokki, Cairo, Egypt
| | - Riham M Aly
- Department of Basic Dental Science, Oral and Dental Research Institute, National Research Centre, 33 El Buhouth St., Dokki, Cairo, 12622, Egypt.
- Stem Cell Laboratory, Center of Excellence for Advanced Sciences, National Research Centre, Cairo, Egypt.
| | - Mostafa Gheith
- National Institute of Laser Enhanced Sciences, Cairo University, Giza, Egypt
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Poblano-Pérez LI, Castro-Manrreza ME, González-Alva P, Fajardo-Orduña GR, Montesinos JJ. Mesenchymal Stromal Cells Derived from Dental Tissues: Immunomodulatory Properties and Clinical Potential. Int J Mol Sci 2024; 25:1986. [PMID: 38396665 PMCID: PMC10888494 DOI: 10.3390/ijms25041986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 01/30/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Mesenchymal stem/stromal cells (MSCs) are multipotent cells located in different areas of the human body. The oral cavity is considered a potential source of MSCs because they have been identified in several dental tissues (D-MSCs). Clinical trials in which cells from these sources were used have shown that they are effective and safe as treatments for tissue regeneration. Importantly, immunoregulatory capacity has been observed in all of these populations; however, this function may vary among the different types of MSCs. Since this property is of clinical interest for cell therapy protocols, it is relevant to analyze the differences in immunoregulatory capacity, as well as the mechanisms used by each type of MSC. Interestingly, D-MSCs are the most suitable source for regenerating mineralized tissues in the oral region. Furthermore, the clinical potential of D-MSCs is supported due to their adequate capacity for proliferation, migration, and differentiation. There is also evidence for their potential application in protocols against autoimmune diseases and other inflammatory conditions due to their immunosuppressive capacity. Therefore, in this review, the immunoregulatory mechanisms identified at the preclinical level in combination with the different types of MSCs found in dental tissues are described, in addition to a description of the clinical trials in which MSCs from these sources have been applied.
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Affiliation(s)
- Luis Ignacio Poblano-Pérez
- Mesenchymal Stem Cell Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center (IMSS), Mexico City 06720, Mexico; (L.I.P.-P.); (G.R.F.-O.)
| | - Marta Elena Castro-Manrreza
- Immunology and Stem Cells Laboratory, FES Zaragoza, National Autonomous University of Mexico (UNAM), Mexico City 09230, Mexico;
| | - Patricia González-Alva
- Tissue Bioengineering Laboratory, Postgraduate Studies, Research Division, Faculty of Dentistry, National Autonomous University of Mexico (UNAM), Mexico City 04510, Mexico;
| | - Guadalupe R. Fajardo-Orduña
- Mesenchymal Stem Cell Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center (IMSS), Mexico City 06720, Mexico; (L.I.P.-P.); (G.R.F.-O.)
| | - Juan José Montesinos
- Mesenchymal Stem Cell Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center (IMSS), Mexico City 06720, Mexico; (L.I.P.-P.); (G.R.F.-O.)
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Tang W, Huo F, Long J, Zhang S, Tian W. Cellular Senescence in Craniofacial Tissue Regeneration: Inducers, Biomarkers, and Interventions. TISSUE ENGINEERING. PART B, REVIEWS 2024; 30:128-141. [PMID: 37565284 DOI: 10.1089/ten.teb.2023.0136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/12/2023]
Abstract
Craniofacial defects and dental tissue loss have significant negative impacts on the structure and function of jaws and face, often resulting in psychological issues in patients, emphasizing the urgent need for effective craniofacial tissue reconstruction. Unfortunately, natural regeneration of these tissues is limited. Dental-derived mesenchymal stem cells (MSCs) have emerged as a promising resource for tissue engineering-based therapeutic approaches. However, the clinical outcomes of MSC-based transplantation have not met expectations due to various complex reasons, and cellular senescence is recognized as one of the potential mechanisms contributing to the suboptimal results. The quality of MSC decreases during large-scale in vitro expansion, and it is also influenced by the age and the health status of donors. To address these challenges, extensive efforts have been made to developing strategies to combat senescence in tissue engineering, leveraging on current knowledge of underlying mechanisms. This review aims to elucidate the impact of cell senescence in craniofacial and dental regeneration and provides an overview of state-of-the-art antisenescence strategies. We first discuss the potential factors that trigger cell senescence in craniofacial tissue engineering. Then we describe senescence biomarkers, monitoring methods for senescent MSCs, and their underlying molecular mechanisms. The primary focus of this review is on current strategies to inhibit and alleviate cell senescence in tissue engineering. We summarize the strategies concerning the prevention of cell senescence, senolysis, modulation of the senescent associated secretory phenotype, and reversal of senescent MSCs, offering promising opportunities to overcome the challenges associated with cell senescence in craniofacial tissue engineering.
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Affiliation(s)
- Weibing Tang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China
| | - Fangjun Huo
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China
| | - Jie Long
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China
| | - Siyuan Zhang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China
| | - Weidong Tian
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China
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20
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Cao C, Maska B, Malik MA, Tagett R, Kaigler D. Immunomodulatory differences between mesenchymal stem cells from different oral tissues. Heliyon 2024; 10:e23317. [PMID: 38192855 PMCID: PMC10771986 DOI: 10.1016/j.heliyon.2023.e23317] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 11/24/2023] [Accepted: 11/30/2023] [Indexed: 01/10/2024] Open
Abstract
Mesenchymal stem cells (MSCs) have recently been identified as having potentially therapeutic immunomodulatory properties. MSCs isolated from different oral tissues have similar morphology and immunophenotypes, however, direct comparisons of their gene expression and immunomodulatory properties have not been conducted. We isolated alveolar bone-derived MSCs (aBMSCs), dental pulp stem cells (DPSCs) and gingiva-derived MSCs (GMSCs) from the same patients and compared their immunophenotypes and transcriptomes. Additionally, we compared their production of soluble immunomodulatory cytokines as well as their immunoregulatory properties in coculture with THP-1 human monocytic cells. RNA sequencing revealed distinct gene expression in DPSCs while aBMSCs and GMSCs had less differentially expressed genes. DPSCs also had significantly less secretion of osteopontin compared to aBMSCs and GMSCs. Finally, DPSCs did not exhibit an immunosuppresive effect on THP-1 cells to the same degree as aBMSCs and GMSCs. These findings demonstrate that MSCs from different oral tissues have distinct transcriptomes and immunoregulatory properties.
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Affiliation(s)
- Chen Cao
- Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA
| | - Bartosz Maska
- Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA
| | - Malika A. Malik
- Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA
| | - Rebecca Tagett
- Bioinformatics Core, Medical School, University of Michigan, Ann Arbor, MI, USA
| | - Darnell Kaigler
- Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA
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21
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Tolouei AE, Oruji F, Tehrani S, Rezaei S, Mozaffari A, Jahri M, Nasiri K. Gingival mesenchymal stem cell therapy, immune cells, and immunoinflammatory application. Mol Biol Rep 2023; 50:10461-10469. [PMID: 37904011 DOI: 10.1007/s11033-023-08826-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 09/12/2023] [Indexed: 11/01/2023]
Abstract
MSC-based therapeutic strategies have proven to be incredibly effective. Robust self-renewal, multilineage differentiation, and potential for tissue regeneration and disease treatments are all features of MSCs isolated from oral tissue. Human exfoliated deciduous teeth, dental follicles, dental pulp, apical papilla SCs, and alveolar bone are the primary sources of oral MSC production. The early immunoinflammatory response is the first stage of the healing process. Oral MSCs can interact with various cells, such as immune cells, revealing potential immunomodulatory regulators. They also have strong differentiation and regeneration potential. Therefore, a ground-breaking strategy would be to research novel immunomodulatory approaches for treating disease and tissue regeneration that depend on the immunomodulatory activities of oral MSCs during tissue regeneration.
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Affiliation(s)
| | - Farshid Oruji
- College of Medicine, Department of Genetics Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA
| | - Sahar Tehrani
- Department of Pediatric Dentistry, School of Dentistry, Ahvaz Jundishapour University of Medical Sciences Ahvaz, Ahvaz, Iran
| | - Sara Rezaei
- Restorative Dentistry Resident, Faculty of Dentistry, Kerman University of Medical Sciences, Kerman, Iran
| | - Asieh Mozaffari
- Department of Periodontics, Faculty of Dentistry, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Mohammad Jahri
- Dental Research Center, Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Kamyar Nasiri
- Department of Dentistry, Islamic Azad University, Tehran, Iran.
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22
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Syahruddin MH, Anggraeni R, Ana ID. A microfluidic organ-on-a-chip: into the next decade of bone tissue engineering applied in dentistry. Future Sci OA 2023; 9:FSO902. [PMID: 37753360 PMCID: PMC10518836 DOI: 10.2144/fsoa-2023-0061] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 08/21/2023] [Indexed: 09/28/2023] Open
Abstract
A comprehensive understanding of the complex physiological and pathological processes associated with alveolar bones, their responses to different therapeutics strategies, and cell interactions with biomaterial becomes necessary in precisely treating patients with severe progressive periodontitis, as a bone-related issue in dentistry. However, existing monolayer cell culture or pre-clinical models have been unable to mimic the complex physiological, pathological and regeneration processes in the bone microenvironment in response to different therapeutic strategies. In this point, 'organ-on-a-chip' (OOAC) technology, specifically 'alveolar-bone-on-a-chip', is expected to resolve the problems by better imitating infection site microenvironment and microphysiology within the oral tissues. The OOAC technology is assessed in this study toward better approaches in disease modeling and better therapeutics strategy for bone tissue engineering applied in dentistry.
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Affiliation(s)
- Muhammad Hidayat Syahruddin
- Postgraduate Student, Dental Science Doctoral Study Program, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
| | - Rahmi Anggraeni
- Research Center for Preclinical & Clinical Medicine, National Research & Innovation Agency of the Republic of Indonesia, Cibinong Science Center, Bogor, 16915, Indonesia
- Research Collaboration Center for Biomedical Scaffolds, National Research & Innovation Agency (BRIN) – Universitas Gadjah Mada (UGM), Yogyakarta, 55281, Indonesia
| | - Ika Dewi Ana
- Department of Dental Biomedical Sciences, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
- Research Collaboration Center for Biomedical Scaffolds, National Research & Innovation Agency (BRIN) – Universitas Gadjah Mada (UGM), Yogyakarta, 55281, Indonesia
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23
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Santilli F, Fabrizi J, Martellucci S, Santacroce C, Iorio E, Pisanu ME, Chirico M, Lancia L, Pulcini F, Manganelli V, Sorice M, Delle Monache S, Mattei V. Lipid rafts mediate multilineage differentiation of human dental pulp-derived stem cells (DPSCs). Front Cell Dev Biol 2023; 11:1274462. [PMID: 38020931 PMCID: PMC10665896 DOI: 10.3389/fcell.2023.1274462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 10/23/2023] [Indexed: 12/01/2023] Open
Abstract
Cell outer membranes contain glycosphingolipids and protein receptors, which are integrated into glycoprotein domains, known as lipid rafts, which are involved in a variety of cellular processes, including receptor-mediated signal transduction and cellular differentiation process. In this study, we analyzed the lipidic composition of human Dental Pulp-Derived Stem Cells (DPSCs), and the role of lipid rafts during the multilineage differentiation process. The relative quantification of lipid metabolites in the organic fraction of DPSCs, performed by Nuclear Magnetic Resonance (NMR) spectroscopy, showed that mono-unsaturated fatty acids (MUFAs) were the most representative species in the total pool of acyl chains, compared to polyunsatured fatty acids (PUFAs). In addition, the stimulation of DPSCs with different culture media induces a multilineage differentiation process, determining changes in the gangliosides pattern. To understand the functional role of lipid rafts during multilineage differentiation, DPSCs were pretreated with a typical lipid raft affecting agent (MβCD). Subsequently, DPSCs were inducted to differentiate into osteoblast, chondroblast and adipoblast cells with specific media. We observed that raft-affecting agent MβCD prevented AKT activation and the expression of lineage-specific mRNA such as OSX, PPARγ2, and SOX9 during multilineage differentiation. Moreover, this compound significantly prevented the tri-lineage differentiation induced by specific stimuli, indicating that lipid raft integrity is essential for DPSCs differentiation. These results suggest that lipid rafts alteration may affect the signaling pathway activated, preventing multilineage differentiation.
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Affiliation(s)
- Francesca Santilli
- Biomedicine and Advanced Technologies Rieti Center, “Sabina Universitas”, Rieti, Italy
| | - Jessica Fabrizi
- Biomedicine and Advanced Technologies Rieti Center, “Sabina Universitas”, Rieti, Italy
- Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Stefano Martellucci
- Biomedicine and Advanced Technologies Rieti Center, “Sabina Universitas”, Rieti, Italy
| | - Costantino Santacroce
- Biomedicine and Advanced Technologies Rieti Center, “Sabina Universitas”, Rieti, Italy
| | - Egidio Iorio
- High Resolution NMR Unit, Core Facilities, Istituto Superiore di Sanità, Rome, Italy
| | - Maria Elena Pisanu
- High Resolution NMR Unit, Core Facilities, Istituto Superiore di Sanità, Rome, Italy
| | - Mattea Chirico
- High Resolution NMR Unit, Core Facilities, Istituto Superiore di Sanità, Rome, Italy
| | - Loreto Lancia
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
| | - Fanny Pulcini
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
| | - Valeria Manganelli
- Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Maurizio Sorice
- Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Simona Delle Monache
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
| | - Vincenzo Mattei
- Dipartimento di Scienze della Vita, della Salute e delle Professioni Sanitarie, Link Campus University, Rome, Italy
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24
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Xing WB, Wu ST, Wang XX, Li FY, Wang RX, He JH, Fu J, He Y. Potential of dental pulp stem cells and their products in promoting peripheral nerve regeneration and their future applications. World J Stem Cells 2023; 15:960-978. [PMID: 37970238 PMCID: PMC10631371 DOI: 10.4252/wjsc.v15.i10.960] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 10/07/2023] [Accepted: 10/23/2023] [Indexed: 10/26/2023] Open
Abstract
Peripheral nerve injury (PNI) seriously affects people's quality of life. Stem cell therapy is considered a promising new option for the clinical treatment of PNI. Dental stem cells, particularly dental pulp stem cells (DPSCs), are adult pluripotent stem cells derived from the neuroectoderm. DPSCs have significant potential in the field of neural tissue engineering due to their numerous advantages, such as easy isolation, multidifferentiation potential, low immunogenicity, and low transplant rejection rate. DPSCs are extensively used in tissue engineering and regenerative medicine, including for the treatment of sciatic nerve injury, facial nerve injury, spinal cord injury, and other neurodegenerative diseases. This article reviews research related to DPSCs and their advantages in treating PNI, aiming to summarize the therapeutic potential of DPSCs for PNI and the underlying mechanisms and providing valuable guidance and a foundation for future research.
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Affiliation(s)
- Wen-Bo Xing
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Shu-Ting Wu
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Xin-Xin Wang
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Fen-Yao Li
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Ruo-Xuan Wang
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Ji-Hui He
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Jiao Fu
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Yan He
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- Department of Stomatology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, Hubei Province, China.
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25
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Zhou L, Zhao S, Xing X. Effects of different signaling pathways on odontogenic differentiation of dental pulp stem cells: a review. Front Physiol 2023; 14:1272764. [PMID: 37929208 PMCID: PMC10622672 DOI: 10.3389/fphys.2023.1272764] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 10/02/2023] [Indexed: 11/07/2023] Open
Abstract
Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells that can differentiate into odontoblast-like cells and protect the pulp. The differentiation of DPSCs can be influenced by biomaterials or growth factors that activate different signaling pathways in vitro or in vivo. In this review, we summarized six major pathways involved in the odontogenic differentiation of DPSCs, Wnt signaling pathways, Smad signaling pathways, MAPK signaling pathways, NF-kB signaling pathways, PI3K/AKT/mTOR signaling pathways, and Notch signaling pathways. Various factors can influence the odontogenic differentiation of DPSCs through one or more signaling pathways. By understanding the interactions between these signaling pathways, we can expand our knowledge of the mechanisms underlying the regeneration of the pulp-dentin complex.
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Affiliation(s)
| | | | - Xianghui Xing
- Department of Pediatric Dentistry, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
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26
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Bai X, Cao R, Wu D, Zhang H, Yang F, Wang L. Dental Pulp Stem Cells for Bone Tissue Engineering: A Literature Review. Stem Cells Int 2023; 2023:7357179. [PMID: 37868704 PMCID: PMC10586346 DOI: 10.1155/2023/7357179] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 06/03/2023] [Accepted: 09/19/2023] [Indexed: 10/24/2023] Open
Abstract
Bone tissue engineering (BTE) is a promising approach for repairing and regenerating damaged bone tissue, using stem cells and scaffold structures. Among various stem cell sources, dental pulp stem cells (DPSCs) have emerged as a potential candidate due to their multipotential capabilities, ability to undergo osteogenic differentiation, low immunogenicity, and ease of isolation. This article reviews the biological characteristics of DPSCs, their potential for BTE, and the underlying transcription factors and signaling pathways involved in osteogenic differentiation; it also highlights the application of DPSCs in inducing scaffold tissues for bone regeneration and summarizes animal and clinical studies conducted in this field. This review demonstrates the potential of DPSC-based BTE for effective bone repair and regeneration, with implications for clinical translation.
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Affiliation(s)
- Xiaolei Bai
- Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Ruijue Cao
- Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Danni Wu
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Huicong Zhang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Fan Yang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Linhong Wang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
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27
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Liu ZZ, Huang Y, Hong CG, Wang X, Duan R, Liu JY, He JL, Duan D, Xie H, Lu M. Autologous olfactory mucosa mesenchymal stem cells treatment improves the neural network in chronic refractory epilepsy. Stem Cell Res Ther 2023; 14:237. [PMID: 37674249 PMCID: PMC10483711 DOI: 10.1186/s13287-023-03458-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 08/18/2023] [Indexed: 09/08/2023] Open
Abstract
BACKGROUND AND AIMS Refractory epilepsy is also known as drug-resistant epilepsy with limited clinical treatment. Benefitting from its safety and easy availability, olfactory mucosa mesenchymal stem cells (OM-MSCs) are considered a preferable MSC source for clinical application. This study aims to investigate whether OM-MSCs are a promising alternative source for treating refractory epilepsy clinically and uncover the mechanism by OM-MSCs administration on an epileptic mouse model. METHODS OM-MSCs were isolated from turbinal and characterized by flow cytometry. Autologous human OM-MSCs treatment on a patient was carried out using intrathecal administration. Epileptic mouse model was established by 1 mg/kg scopolamine and 300 mg/kg pilocarpine treatment (intraperitoneal). Stereotaxic microinjection was employed to deliver the mouse OM-MSCs. Mouse electroencephalograph recording was used to investigate the seizures. Brain structure was evaluated by magnetic resonance imaging (MRI). Immunohistochemical and immunofluorescent staining of GFAP, IBA1, MAP2, TUBB3, OLIG2, CD4, CD25, and FOXP3 was carried out to investigate the neural cells and Treg cells. QRT-PCR and ELISA were performed to determine the cytokines (Il1b, Il6, Tnf, Il10) on mRNA and protein level. Y-maze, the object location test, and novel object recognition test were performed to measure the cognitive function. Footprint test, rotarod test, balance beam test, and grip strength test were conducted to evaluate the locomotive function. Von Frey testing was carried out to assess the mechanical allodynia. RESULTS Many beneficial effects of the OM-MSC treatment on disease status, including seizure type, frequency, severity, duration, and cognitive function, and no apparent adverse effects were observed at the 8-year follow-up case. Brain MRI indicated that autologous OM-MSC treatment alleviated brain atrophy in epilepsy patients. A study in an epileptic mouse model revealed that OM-MSC treatment recruited Treg cells to the brain, inhibited inflammation, rebuilt the neural network, and improved the cognitive, locomotive, and perceptive functions of epileptic mice. CONCLUSIONS Autologous OM-MSC treatment is efficacious for improving chronic refractory epilepsy, suggesting a future therapeutic candidate for epilepsy. TRIAL REGISTRATION The study was registered with Chinese Clinical Trial Registry (ChiCTR2200055357).
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Affiliation(s)
- Zheng-Zhao Liu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Hunan Key Laboratory of Organ Injury, Aging and Regenerative Medicine, Changsha, 410008, Hunan, China
- Hunan Key Laboratory of Bone Joint Degeneration and Injury, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Yan Huang
- NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, 410008, Hunan, China
- Hunan Provincial Key Laboratory of Neurorestoration, Hunan Normal University, Changsha, 410081, Hunan, China
- Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, 410219, Hunan, China
- First Clinical Department of Changsha Medical University, Changsha, 410081, Hunan, China
| | - Chun-Gu Hong
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Xin Wang
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Ran Duan
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Jian-Yang Liu
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Jia-Lin He
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Da Duan
- Department of Neurosurgery, the 921st Hospital of PLA (Second Affiliated Hospital of Hunan Normal University), Changsha, 410081, Hunan, China
| | - Hui Xie
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Hunan Key Laboratory of Organ Injury, Aging and Regenerative Medicine, Changsha, 410008, Hunan, China.
- Hunan Key Laboratory of Bone Joint Degeneration and Injury, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
| | - Ming Lu
- Department of Neurosurgery, the 921st Hospital of PLA (Second Affiliated Hospital of Hunan Normal University), Changsha, 410081, Hunan, China.
- Hunan Provincial Key Laboratory of Neurorestoration, Hunan Normal University, Changsha, 410081, Hunan, China.
- Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, 410219, Hunan, China.
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28
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Yu F, Yao L, Li F, Wang C, Ye L. Releasing YAP dysfunction-caused replicative toxicity rejuvenates mesenchymal stem cells. Aging Cell 2023; 22:e13913. [PMID: 37340571 PMCID: PMC10497818 DOI: 10.1111/acel.13913] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 06/01/2023] [Accepted: 06/08/2023] [Indexed: 06/22/2023] Open
Abstract
Hippo-independent YAP dysfunction has been demonstrated to cause chronological aging of stromal cells by impairing the integrity of nuclear envelope (NE). In parallel with this report, we uncover that YAP activity also controls another type of cellular senescence, the replicative senescence in in vitro expansion of mesenchymal stromal cells (MSCs), but this event is Hippo phosphorylation-dependent, and there exist another NE integrity-independent downstream mechanisms of YAP. Specifically, Hippo phosphorylation causes reduced nuclear/active YAP and then decreases the level of YAP protein in the proceeding of replicative senescence. YAP/TEAD governs RRM2 expression to release replicative toxicity (RT) via licensing G1/S transition. Besides, YAP controls the core transcriptomics of RT to delay the onset of genome instability and enhances DNA damage response/repair. Hippo-off mutations of YAP (YAPS127A/S381A ) satisfactorily release RT via maintaining cell cycle and reducing genome instability, finally rejuvenating MSCs and restoring their regenerative capabilities without risks of tumorigenesis.
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Affiliation(s)
- Fanyuan Yu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral DiseasesWest China Hospital of Stomatology, Sichuan UniversityChengduChina
- Department of Endodontics, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Lin Yao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral DiseasesWest China Hospital of Stomatology, Sichuan UniversityChengduChina
- Department of Endodontics, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Feifei Li
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral DiseasesWest China Hospital of Stomatology, Sichuan UniversityChengduChina
| | - Chenglin Wang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral DiseasesWest China Hospital of Stomatology, Sichuan UniversityChengduChina
- Department of Endodontics, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Ling Ye
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral DiseasesWest China Hospital of Stomatology, Sichuan UniversityChengduChina
- Department of Endodontics, West China Hospital of StomatologySichuan UniversityChengduChina
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29
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Agriesti F, Landini F, Tamma M, Pacelli C, Mazzoccoli C, Calice G, Ruggieri V, Capitanio G, Mori G, Piccoli C, Capitanio N. Bioenergetic profile and redox tone modulate in vitro osteogenesis of human dental pulp stem cells: new perspectives for bone regeneration and repair. Stem Cell Res Ther 2023; 14:215. [PMID: 37608350 PMCID: PMC10463344 DOI: 10.1186/s13287-023-03447-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 08/10/2023] [Indexed: 08/24/2023] Open
Abstract
BACKGROUND Redox signaling and energy metabolism are known to be involved in controlling the balance between self-renewal and proliferation/differentiation of stem cells. In this study we investigated metabolic and redox changes occurring during in vitro human dental pulp stem cells (hDPSCs) osteoblastic (OB) differentiation and tested on them the impact of the reactive oxygen species (ROS) signaling. METHODS hDPSCs were isolated from dental pulp and subjected to alkaline phosphatase and alizarin red staining, q-RT-PCR, and western blotting analysis of differentiation markers to assess achievement of osteogenic/odontogenic differentiation. Moreover, a combination of metabolic flux analysis and confocal cyto-imaging was used to profile the metabolic phenotype and to evaluate the redox tone of hDPSCs. RESULTS In differentiating hDPSCs we observed the down-regulation of the mitochondrial respiratory chain complexes expression since the early phase of the process, confirmed by metabolic flux analysis, and a reduction of the basal intracellular peroxide level in its later phase. In addition, dampened glycolysis was observed, thereby indicating a lower energy-generating phenotype in differentiating hDPSCs. Treatment with the ROS scavenger Trolox, applied in the early-middle phases of the process, markedly delayed OB differentiation of hDPSCs assessed as ALP activity, Runx2 expression, mineralization capacity, expression of stemness and osteoblast marker genes (Nanog, Lin28, Dspp, Ocn) and activation of ERK1/2. In addition, the antioxidant partly prevented the inhibitory effect on cell metabolism observed following osteogenic induction. CONCLUSIONS Altogether these results provided evidence that redox signaling, likely mediated by peroxide species, influenced the stepwise osteogenic expansion/differentiation of hDPSCs and contributed to shape its accompanying metabolic phenotype changes thus improving their efficiency in bone regeneration and repair.
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Affiliation(s)
- Francesca Agriesti
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
- Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
| | - Francesca Landini
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Mirko Tamma
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Consiglia Pacelli
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Carmela Mazzoccoli
- Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
| | - Giovanni Calice
- Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
| | - Vitalba Ruggieri
- Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
- Clinical Pathology Unit, “Madonna delle Grazie’’ Hospital, Matera, Italy
| | - Giuseppe Capitanio
- Department of Translational Biomedicine and Neuroscience “DiBraiN”, University of Bari “Aldo Moro”, 70124 Bari, Italy
| | - Giorgio Mori
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Claudia Piccoli
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Nazzareno Capitanio
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
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30
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Yang D, Solidum JGN, Park D. Dental Pulp Stem Cells and Current in vivo Approaches to Study Dental Pulp Stem Cells in Pulp Injury and Regeneration. J Bone Metab 2023; 30:231-244. [PMID: 37718901 PMCID: PMC10509030 DOI: 10.11005/jbm.2023.30.3.231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 08/20/2023] [Indexed: 09/19/2023] Open
Abstract
Dental pulp stem cells (DPSCs) have garnered significant interest in dental research for their unique characteristics and potential in tooth development and regeneration. While there were many studies to define their stem cell-like characteristics and osteogenic differentiation functions that are considered ideal candidates for regenerating damaged dental pulp tissue, how endogenous DPSCs respond to dental pulp injury and supply new dentin-forming cells has not been extensively investigated in vivo. Here, we review the recent progress in identity, function, and regulation of endogenous DPSCs and their clinical potential for pulp injury and regeneration. In addition, we discuss current advances in new mouse models, imaging techniques, and its practical uses and limitations in the analysis of DPSCs in pulp injury and regeneration in vivo.
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Affiliation(s)
- Dongwook Yang
- Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX,
USA
- Center for Skeletal Biology, Baylor College of Medicine, Houston, TX,
USA
| | - Jea Giezl Niedo Solidum
- Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX,
USA
- Department of Biochemistry & Molecular Biology, College of Medicine, University of the Philippines Manila, Manila,
Philippines
| | - Dongsu Park
- Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX,
USA
- Center for Skeletal Biology, Baylor College of Medicine, Houston, TX,
USA
- Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX,
USA
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31
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Mélou C, Pellen-Mussi P, Novello S, Brézulier D, Novella A, Tricot S, Bellaud P, Chauvel-Lebret D. Spheroid Culture System, a Promising Method for Chondrogenic Differentiation of Dental Mesenchymal Stem Cells. Biomedicines 2023; 11:biomedicines11051314. [PMID: 37238984 DOI: 10.3390/biomedicines11051314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/24/2023] [Accepted: 04/25/2023] [Indexed: 05/28/2023] Open
Abstract
The objective of the present work was to develop a three-dimensional culture model to evaluate, in a short period of time, cartilage tissue engineering protocols. The spheroids were compared with the gold standard pellet culture. The dental mesenchymal stem cell lines were from pulp and periodontal ligament. The evaluation used RT-qPCR and Alcian Blue staining of the cartilage matrix. This study showed that the spheroid model allowed for obtaining greater fluctuations of the chondrogenesis markers than for the pellet one. The two cell lines, although originating from the same organ, led to different biological responses. Finally, biological changes were detectable for short periods of time. In summary, this work demonstrated that the spheroid model is a valuable tool for studying chondrogenesis and the mechanisms of osteoarthritis, and evaluating cartilage tissue engineering protocols.
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Affiliation(s)
- Caroline Mélou
- CNRS, ISCR (Institut des Sciences Chimiques de Rennes), University of Rennes, UMR 6226, 35000 Rennes, France
- Pôle d'Odontologie, Centre Hospitalier Universitaire de Rennes, 35033 Rennes, France
- UFR Odontologie, University of Rennes, 35043 Rennes, France
| | - Pascal Pellen-Mussi
- CNRS, ISCR (Institut des Sciences Chimiques de Rennes), University of Rennes, UMR 6226, 35000 Rennes, France
| | - Solen Novello
- CNRS, ISCR (Institut des Sciences Chimiques de Rennes), University of Rennes, UMR 6226, 35000 Rennes, France
- Pôle d'Odontologie, Centre Hospitalier Universitaire de Rennes, 35033 Rennes, France
- UFR Odontologie, University of Rennes, 35043 Rennes, France
| | - Damien Brézulier
- CNRS, ISCR (Institut des Sciences Chimiques de Rennes), University of Rennes, UMR 6226, 35000 Rennes, France
- Pôle d'Odontologie, Centre Hospitalier Universitaire de Rennes, 35033 Rennes, France
| | - Agnès Novella
- CNRS, ISCR (Institut des Sciences Chimiques de Rennes), University of Rennes, UMR 6226, 35000 Rennes, France
| | - Sylvie Tricot
- CNRS, ISCR (Institut des Sciences Chimiques de Rennes), University of Rennes, UMR 6226, 35000 Rennes, France
| | - Pascale Bellaud
- CNRS, Inserm UMS Biosit, France BioImaging, Core Facility H2P2, University of Rennes, 35000 Rennes, France
| | - Dominique Chauvel-Lebret
- CNRS, ISCR (Institut des Sciences Chimiques de Rennes), University of Rennes, UMR 6226, 35000 Rennes, France
- Pôle d'Odontologie, Centre Hospitalier Universitaire de Rennes, 35033 Rennes, France
- UFR Odontologie, University of Rennes, 35043 Rennes, France
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Uribe-Etxebarria V, Pineda JR, García-Gallastegi P, Agliano A, Unda F, Ibarretxe G. Notch and Wnt Signaling Modulation to Enhance DPSC Stemness and Therapeutic Potential. Int J Mol Sci 2023; 24:ijms24087389. [PMID: 37108549 PMCID: PMC10138690 DOI: 10.3390/ijms24087389] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/16/2023] [Accepted: 04/16/2023] [Indexed: 04/29/2023] Open
Abstract
The Dental Pulp of permanent human teeth is home to stem cells with remarkable multilineage differentiation ability: human Dental Pulp Stem Cells (DPSCs). These cells display a very notorious expression of pluripotency core factors, and the ability to give rise to mature cell lineages belonging to the three embryonic layers. For these reasons, several researchers in the field have long considered human DPSCs as pluripotent-like cells. Notably, some signaling pathways such as Notch and Wnt contribute to maintaining the stemness of these cells through a complex network involving metabolic and epigenetic regulatory mechanisms. The use of recombinant proteins and selective pharmacological modulators of Notch and Wnt pathways, together with serum-free media and appropriate scaffolds that allow the maintenance of the non-differentiated state of hDPSC cultures could be an interesting approach to optimize the potency of these stem cells, without a need for genetic modification. In this review, we describe and integrate findings that shed light on the mechanisms responsible for stemness maintenance of hDPSCs, and how these are regulated by Notch/Wnt activation, drawing some interesting parallelisms with pluripotent stem cells. We summarize previous work on the stem cell field that includes interactions between epigenetics, metabolic regulations, and pluripotency core factor expression in hDPSCs and other stem cell types.
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Affiliation(s)
| | - Jose Ramon Pineda
- Cell Biology and Histology Department, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain
- Achucarro Basque Center for Neuroscience Fundazioa Leioa, Sede Building, 3rd Floor, 48940 Leioa, Spain
| | - Patricia García-Gallastegi
- Physiology Department, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain
| | - Alice Agliano
- Division of Radiotherapy and Imaging, Cancer Research UK Cancer Imaging Centre, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London SW7 3RP, UK
- Department of Materials and Department of Bioengineering, Institute of Biomedical Engineering, Imperial College London, Exhibition Road, London SW7 2AZ, UK
| | - Fernando Unda
- Cell Biology and Histology Department, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain
| | - Gaskon Ibarretxe
- Cell Biology and Histology Department, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain
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Iranmanesh P, Vedaei A, Salehi-Mazandarani S, Nikpour P, Khazaei S, Khademi A, Galler KM, Nekoofar MH, Dummer PMH. MicroRNAs-mediated regulation of the differentiation of dental pulp-derived mesenchymal stem cells: a systematic review and bioinformatic analysis. Stem Cell Res Ther 2023; 14:76. [PMID: 37038220 PMCID: PMC10088330 DOI: 10.1186/s13287-023-03289-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 03/16/2023] [Indexed: 04/12/2023] Open
Abstract
BACKGROUND Human dental pulp-derived mesenchymal stem cells (hDP-MSCs), which include human dental pulp stem cells (hDPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs), are promising cell sources for regenerative therapies. Nevertheless, a lack of knowledge relating to the mechanisms regulating their differentiation has limited their clinical application. microRNAs (miRNAs) are important regulatory molecules in cellular processes including cell differentiation. This systematic review aims to provide a panel of miRNAs that regulate the differentiation of hDP-MSCs including hDPSCs and SHEDs. Additionally, bioinformatic analyses were conducted to discover target genes, signaling pathways and gene ontologies associated with the identified miRNAs. METHODS A literature search was performed in MEDLINE (via PubMed), Web of Science, Scopus, Embase and Cochrane Library. Experimental studies assessing the promotive/suppressive effect of miRNAs on the differentiation of hDP-MSCs and studies evaluating changes to the expression of miRNAs during the differentiation of hDP-MSCs were included. miRNAs involved in odontogenic/osteogenic differentiation were then included in a bioinformatic analysis. A miRNA-mRNA network was constructed, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. A protein-protein interaction (PPI) network was also constructed. RESULTS Of 766 initially identified records through database searching, 42 and 36 studies were included in qualitative synthesis and bioinformatic analyses, respectively. Thirteen miRNAs promoted and 17 suppressed odontogenic/osteogenic differentiation of hDP-MSCs. hsa-miR-140-5p, hsa-miR-218 and hsa-miR-143 were more frequently reported suppressing the odontogenic/osteogenic differentiation of hDP-MSCs. hsa-miR-221 and hsa-miR-124 promoted and hsa-miR-140-5p inhibited neuronal differentiation, hsa-miR-26a-5p promoted and hsa-miR-424 suppressed angiogenic differentiation, and hsa-miR-135 and hsa-miR-143 inhibited differentiation within myogenic lineages. A miRNA-mRNA network including 1890 nodes and 2171 edges was constructed. KEGG pathway analysis revealed MAPK, PI3K-Akt and FoxO as key signaling pathways involved in the odontogenic/osteogenic differentiation of hDP-MSCs. CONCLUSIONS The findings of this systematic review support the potential application of the specific miRNAs to regulate the directed differentiation of hDP-MSCs in the field of regenerative therapies.
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Affiliation(s)
- Pedram Iranmanesh
- Dental Research Center, Department of Endodontics, Dental Research Institute, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amirhossein Vedaei
- Student Research Committee, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sadra Salehi-Mazandarani
- Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Parvaneh Nikpour
- Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Saber Khazaei
- Department of Endodontics, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Abbasali Khademi
- Dental Research Center, Department of Endodontics, Dental Research Institute, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Kerstin M. Galler
- Department of Conservative Dentistry and Periodontology, University Hospital Erlangen, Erlangen, Germany
| | - Mohammad-Hossein Nekoofar
- Department of Endodontics, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Department of Endodontics, Bahçeşehir University School of Dentistry, Istanbul, Turkey
| | - Paul M. H. Dummer
- School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
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34
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Hu X, Geng P, Zhao X, Wang Q, Liu C, Guo C, Dong W, Jin X. The NG2-glia is a potential target to maintain the integrity of neurovascular unit after acute ischemic stroke. Neurobiol Dis 2023; 180:106076. [PMID: 36921779 DOI: 10.1016/j.nbd.2023.106076] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 02/07/2023] [Accepted: 03/07/2023] [Indexed: 03/18/2023] Open
Abstract
The neurovascular unit (NVU) plays a critical role in health and disease. In the current review, we discuss the critical role of a class of neural/glial antigen 2 (NG2)-expressing glial cells (NG2-glia) in regulating NVU after acute ischemic stroke (AIS). We first introduce the role of NG2-glia in the formation of NVU during development as well as aging-induced damage to NVU and accompanying NG2-glia change. We then discuss the reciprocal interactions between NG2-glia and the other component cells of NVU, emphasizing the factors that could influence NG2-glia. Damage to the NVU integrity is the pathological basis of edema and hemorrhagic transformation, the most dreaded complication after AIS. The role of NG2-glia in AIS-induced NVU damage and the effect of NG2-glia transplantation on AIS-induced NVU damage are summarized. We next discuss the role of NG2-glia and the effect of NG2-glia transplantation in oligodendrogenesis and white matter repair as well as angiogenesis which is associated with the outcome of the patients after AIS. Finally, we review the current strategies to promote NG2-glia proliferation and differentiation and propose to use the dental pulp stem cells (DPSC)-derived exosome as a promising strategy to reduce AIS-induced injury and promote repair through maintaining the integrity of NVU by regulating endogenous NG2-glia proliferation and differentiation.
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Affiliation(s)
- Xiaoyan Hu
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Histology and Embryology, School of Basic Medical Sciences, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China
| | - Panpan Geng
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Histology and Embryology, School of Basic Medical Sciences, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China
| | - Xiaoyun Zhao
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Histology and Embryology, School of Basic Medical Sciences, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China
| | - Qian Wang
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Histology and Embryology, School of Basic Medical Sciences, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China
| | - Changqing Liu
- Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing, China
| | - Chun Guo
- School of Biosciences, University of Sheffield, Firth Court, Western Bank, Sheffield, UK
| | - Wen Dong
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
| | - Xinchun Jin
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Histology and Embryology, School of Basic Medical Sciences, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China; Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
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35
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Salkin H, Acar MB, Gonen ZB, Basaran KE, Ozcan S. Comparative proteomics analysis of transforming growth factor-beta1-overexpressed human dental pulp stem cell-derived secretome on CD44-mediated fibroblast activation via canonical smad signal pathway. Connect Tissue Res 2023; 64:205-218. [PMID: 36421034 DOI: 10.1080/03008207.2022.2144733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE The aim of this study investigates whether the secretome collected from human dental pulp stem cells (hDPSCs) transfected with transforming growth factor-beta1 (TGF-β1) is related to CD44 expression of fibroblasts and canonical smad signaling pathway via proteomic analyzes. MATERIALS AND METHODS In order to obtain secretome, hDPSCs were conditioned with serum-free alpha-MEM in an incubator containing 37°C, 5% CO2, and humidity for 18-24 h. Proteins in control and TGF-β1 secretome were analyzed by tandem mass spectrometry-based shotgun proteomic method. Bioinformatic evaluations were completed via Ingenuity Pathway Analysis (IPA, QIAGEN) software. CD44 expressions in fibroblasts were evaluated by real time-PCR, western blot, and immunofluorescent staining. The relationship of canonical smad pathway and CD44 was analyzed by western blot and LC-MS/MS. Cell cycle, proliferation and wound healing tests were performed in the secretome groups. RESULTS Venn diagram was showed 174 common proteins were identified from each group. In the control secretome 140 unique proteins were identified and 66 entries were exclusive for TGF-β1 secretome. CD44 gene and protein expressions were increased in fibroblasts treated with TGF-β1 secretome. Relationship between targeted protein data showed that activation of the canonical TGF-β1/Smad pathway was up-regulated CD44 expression in fibroblasts. The canonical smad pathway-mediated upregulation of CD44 may increase the mitotic activity, proliferation, and wound healing potential in fibroblasts. CONCLUSION While TGF-β1-transfected hDPSC secretome may be a potential therapeutic candidate in regenerative connective tissue therapies as it induces fibroblast activation, anti-TGF-β1-based therapies would be considered in histopathological conditions such as pulmonary fibrosis or hepatic fibrosis.
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Affiliation(s)
- H Salkin
- Vocational School, Department of Medical Services and Techniques, Program of Pathology Laboratory Techniques, Beykent University, Istanbul, Turkey
| | - M B Acar
- Genome and Stem Cell Center, Erciyes University, Kayseri, Turkey
| | - Z B Gonen
- Genome and Stem Cell Center, Erciyes University, Kayseri, Turkey
| | - K E Basaran
- Department of Physiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - S Ozcan
- Department of Biology, Faculty of Science, Erciyes University, Kayseri, Turkey
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36
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Chen H, Huang Z, Chen C. The Role of Histone Acetylation Modification in Dental Tissue-Derived Mesenchymal Stem Cells and Odontogenesis. Cell Reprogram 2023; 25:11-19. [PMID: 36594932 DOI: 10.1089/cell.2022.0091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Odontogenesis is a complex physiological process that is based on dental tissue-derived mesenchymal stem cells (MSCs). Dental tissue-derived MSCs are the stem cell populations isolated and characterized from different parts of the oral cavity, and are considered as promising candidates for stem cell-based therapy. During odontogenesis, epigenetic factors can influence the proliferation, differentiation, or apoptosis of dental tissue-derived MSCs. As one of the epigenetic modifications, histone acetylation modification is critical for the proper regulation of many biological processes, including transcriptional regulation of cell cycle progression and cell fate. In odontogenesis, histone acetylation and deacetylation play crucial roles in odontogenic differentiation of dental tissue-derived MSCs. In this review, we aim to outline the general features of acetylation modification and describe their roles in odontogenic differentiation of dental tissue-derived MSCs, as well as their future implications in the field of novel regenerative therapies for the dentine-pulp complex.
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Affiliation(s)
- Haoling Chen
- Department of Pediatric Dentistry, Stomatological Hospital, Southern Medical University, Guangzhou, China
| | - Zijing Huang
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, China
| | - Chuxiao Chen
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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37
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Amato M, Santonocito S, Viglianisi G, Tatullo M, Isola G. Impact of Oral Mesenchymal Stem Cells Applications as a Promising Therapeutic Target in the Therapy of Periodontal Disease. Int J Mol Sci 2022; 23:13419. [PMID: 36362206 PMCID: PMC9658889 DOI: 10.3390/ijms232113419] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/26/2022] [Accepted: 10/31/2022] [Indexed: 11/06/2022] Open
Abstract
Periodontal disease is a chronic inflammatory condition affecting about 20-50% of people, worldwide, and manifesting clinically through the detection of gingival inflammation, clinical attachment loss, radiographically assessed resorption of alveolar bone, gingival bleeding upon probing, teeth mobility and their potential loss at advanced stages. It is characterized by a multifactorial etiology, including an imbalance of the oral microbiota, mechanical stress and systemic diseases such as diabetes mellitus. The current standard treatments for periodontitis include eliminating the microbial pathogens and applying biomaterials to treat the bone defects. However, periodontal tissue regeneration via a process consistent with the natural tissue formation process has not yet been achieved. Developmental biology studies state that periodontal tissue is composed of neural crest-derived ectomesenchyme. The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing the relevant literature that assesses the periodontal-regenerative potential of stem cells.
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Affiliation(s)
- Mariacristina Amato
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
| | - Simona Santonocito
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
| | - Gaia Viglianisi
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
| | - Marco Tatullo
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, 70122 Bari, Italy
| | - Gaetano Isola
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
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38
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Lazăr L, Manu DR, Dako T, Mârțu MA, Suciu M, Ormenișan A, Păcurar M, Lazăr AP. Effects of Laser Application on Alveolar Bone Mesenchymal Stem Cells and Osteoblasts: An In Vitro Study. Diagnostics (Basel) 2022; 12:diagnostics12102358. [PMID: 36292047 PMCID: PMC9600660 DOI: 10.3390/diagnostics12102358] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 09/20/2022] [Accepted: 09/26/2022] [Indexed: 12/03/2022] Open
Abstract
Mesenchymal stem cells isolated from the bone marrow have a great differentiation potential, being able to produce many cell lines, including osteoblasts. Osteoblasts have an important role in bone remodeling by actively participating in the maturation and mineralization of the extracellular matrix. The aim of this study was to determine the effect of laser application on the viability and proliferation of osteoblasts. Methods: Alveolar bone was harvested from 8 patients and placed into a culture medium to induce proliferation of mesenchymal stem cells. These were differentiated into osteoblasts in special conditions. The cells from each patient were split into two groups, one was treated using a 980 nm laser (1W output power, pulsed mode, 20 s, 50 mm distance) (laser “+”) and the other one did not receive laser stimulation (laser “-”). Results: Using the confocal microscope, we determined that the cells from the laser “+” group were more active when compared to the laser “-” group. The number of cells in the laser “+” group was significantly greater compared to the laser “-” group as the ImageJ-NIH software showed (p = 0.0072). Conclusions: Laser application increases the proliferation rate of osteoblasts and intensifies their cellular activity.
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Affiliation(s)
- Luminița Lazăr
- Department of Periodontology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mures, 38 Ghe. Marinescu Street, 540139 Târgu Mures, Romania
| | - Doina Ramona Manu
- Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Târgu Mures, Romania
| | - Timea Dako
- Department of Odontology and Oral Pathology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mures, 38 Ghe. Marinescu Street, 540139 Târgu Mures, Romania
- Correspondence: (T.D.); (M.-A.M.); Tel.: +40-740629857 (T.D.)
| | - Maria-Alexandra Mârțu
- Department of Periodontology, Grigore T. Popa University of Medicine and Pharmacy Iasi, Universitatii Street 16, 700115 Iasi, Romania
- Correspondence: (T.D.); (M.-A.M.); Tel.: +40-740629857 (T.D.)
| | - Mircea Suciu
- Department of Oral Rehabilitation and Occlusology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mures, 38 Ghe. Marinescu Street, 540139 Târgu Mures, Romania
| | - Alina Ormenișan
- Department of Oral and Maxillofacial Surgery, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mures, 38 Ghe. Marinescu Street, 540139 Târgu Mures, Romania
| | - Mariana Păcurar
- Department of Orthodontics, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mures, 38 Ghe. Marinescu Street, 540139 Târgu Mures, Romania
| | - Ana-Petra Lazăr
- Institution Organizing University Doctoral Studies (I. O. S. U. D.), George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureş, 38 Ghe. Marinescu Street, 540139 Târgu Mures, Romania
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Ahuja A, Tyagi PK, Kumar M, Sharma N, Prakash S, Radha, Chandran D, Dhumal S, Rais N, Singh S, Dey A, Senapathy M, Saleena LAK, Shanavas A, Mohankumar P, Rajalingam S, Murugesan Y, Vishvanathan M, Sathyaseelan SK, Viswanathan S, Kumar KK, Natta S, Mekhemar M. Botanicals and Oral Stem Cell Mediated Regeneration: A Paradigm Shift from Artificial to Biological Replacement. Cells 2022; 11:2792. [PMID: 36139367 PMCID: PMC9496740 DOI: 10.3390/cells11182792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 09/03/2022] [Accepted: 09/04/2022] [Indexed: 11/23/2022] Open
Abstract
Stem cells are a well-known autologous pluripotent cell source, having excellent potential to develop into specialized cells, such as brain, skin, and bone marrow cells. The oral cavity is reported to be a rich source of multiple types of oral stem cells, including the dental pulp, mucosal soft tissues, periodontal ligament, and apical papilla. Oral stem cells were useful for both the regeneration of soft tissue components in the dental pulp and mineralized structure regeneration, such as bone or dentin, and can be a viable substitute for traditionally used bone marrow stem cells. In recent years, several studies have reported that plant extracts or compounds promoted the proliferation, differentiation, and survival of different oral stem cells. This review is carried out by following the PRISMA guidelines and focusing mainly on the effects of bioactive compounds on oral stem cell-mediated dental, bone, and neural regeneration. It is observed that in recent years studies were mainly focused on the utilization of oral stem cell-mediated regeneration of bone or dental mesenchymal cells, however, the utility of bioactive compounds on oral stem cell-mediated regeneration requires additional assessment beyond in vitro and in vivo studies, and requires more randomized clinical trials and case studies.
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Affiliation(s)
- Anami Ahuja
- Department of Biotechnology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow 226031, India
- Department of Biotechnology, Meerut Institute of Engineering and Technology, Meerut 250005, India
| | - Pankaj Kumar Tyagi
- Department of Biotechnology, Noida Institute of Engineering & Technology, Greater Noida 201306, India
| | - Manoj Kumar
- Chemical and Biochemical Processing Division, ICAR–Central Institute for Research on Cotton Technology, Mumbai 400019, India
| | - Naveen Sharma
- Division of Biomedical Informatics, Indian Council of Medical Research, New Delhi 110029, India
| | - Suraj Prakash
- School of Biological and Environmental Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229, India
| | - Radha
- School of Biological and Environmental Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229, India
| | - Deepak Chandran
- Department of Veterinary Sciences and Animal Husbandry, Amrita School of Agricultural Sci-ences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Sangram Dhumal
- Division of Horticulture, RCSM College of Agriculture, Kolhapur 416004, India
| | - Nadeem Rais
- Department of Pharmacy, Bhagwant University, Ajmer 305004, India
| | - Surinder Singh
- Dr. S. S. Bhatnagar University Institute of Chemical Engineering and Technology, Panjab University, Chandigarh 160014, India
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata 700073, India
| | - Marisennayya Senapathy
- Department of Rural Development and Agricultural Extension, College of Agriculture, Wolaita Sodo University, Wolaita Sodo P.O. Box 138, Ethiopia
| | - Lejaniya Abdul Kalam Saleena
- Department of Food Science and Nutrition, Faculty of Applied Sciences, UCSI University, Kuala Lampur 56000, Malaysia
| | - Arjun Shanavas
- Division of Medicine, Indian Veterinary Research Institute, Bareilly 243122, India
| | - Pran Mohankumar
- School of Agriculture and Biosciences, Karunya Institute of Technology and Sciences, Coimbatore 641114, India
| | - Sureshkumar Rajalingam
- Department of Agronomy, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Yasodha Murugesan
- Department of Agronomy, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Marthandan Vishvanathan
- Department of Seed Science and Technology, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | | | - Sabareeshwari Viswanathan
- Department of Soil Science and Agricultural Chemistry, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Keerthana Krishna Kumar
- Department of Soil Science and Agricultural Chemistry, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Suman Natta
- ICAR—National Research Centre for Orchids, Pakyong 737106, India
| | - Mohamed Mekhemar
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Chris-tian-Albrecht’s University, 24105 Kiel, Germany
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Ma J, Lei P, Chen H, Wang L, Fang Y, Yan X, Yang Q, Peng B, Jin L, Sun D. Advances in lncRNAs from stem cell-derived exosome for the treatment of cardiovascular diseases. Front Pharmacol 2022; 13:986683. [PMID: 36147326 PMCID: PMC9486024 DOI: 10.3389/fphar.2022.986683] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 08/12/2022] [Indexed: 11/21/2022] Open
Abstract
Cardiovascular diseases (CVDs) are the leading cause of mortality globally. Benefiting from the advantages of early diagnosis and precision medicine, stem cell-based therapies have emerged as promising treatment options for CVDs. However, autologous or allogeneic stem cell transplantation imposes a potential risk of immunological rejection, infusion toxicity, and oncogenesis. Fortunately, exosome can override these limitations. Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) in exosome from stem cell paracrine factors play critical roles in stem cell therapy and participate in numerous regulatory processes, including transcriptional silencing, transcriptional activation, chromosome modification, and intranuclear transport. Accordingly, lncRNAs can treat CVDs by directly acting on specific signaling pathways. This mini review systematically summarizes the key regulatory actions of lncRNAs from different stem cells on myocardial aging and apoptosis, ischemia-reperfusion injury, retinopathy, atherosclerosis, and hypertension. In addition, the current challenges and future prospects of lncRNAs treatment for CVDs are discussed.
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Affiliation(s)
- Jiahui Ma
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, China
| | - Pengyu Lei
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, China
| | - Haojie Chen
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, China
| | - Lei Wang
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, China
| | - Yimeng Fang
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, China
| | - Xiaoqing Yan
- Department of Pharmacy, Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China
| | - Qinsi Yang
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China
| | - Bo Peng
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China
| | - Libo Jin
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, China
- *Correspondence: Da Sun, ; Libo Jin,
| | - Da Sun
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, China
- *Correspondence: Da Sun, ; Libo Jin,
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Andrade JMM, Maurmann N, Lopes DV, Pereira DP, Pranke P, Henriques AT. Rosmarinic and chlorogenic acid, isolated from ferns, suppress stem cell damage induced by hydrogen peroxide. J Pharm Pharmacol 2022; 74:1609-1617. [PMID: 36029199 DOI: 10.1093/jpp/rgac061] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 07/25/2022] [Indexed: 11/12/2022]
Abstract
OBJECTIVES Evaluating the effects of rosmarinic (RA) and cryptochlorogenic (CGA) acids isolated from Blechnum binervatum extract on stem cell viability, toxicity and the protective effect on oxidative cell damage. METHODS MTT and LDH methods were employed, using stem cells from teeth. RA and CGA were evaluated at 100, 250 and 500 µM. The negative effect of hydrogen peroxide (H2O2) (200-2200 µM) and the capacity of RA and CGA (10-100 µM) as protective agents were also evaluated. DAPI followed by fluorescent microscopy was employed to photograph the treated and untreated cells. KEY FINDINGS At all tested concentrations, RA and CGA demonstrated the ability to maintain cell viability, and with no cytotoxic effects on the treated stem cells. RA also induced an increase of the cell viability and a reduction in cytotoxicity. H2O2 (1400 µM) induced >50% of cytotoxicity, and both compounds were capable of suppressing H2O2 damage, even at the lowest concentration. At 100 µM, in H2O2 presence, total cell viability was observed through microscope imaging. CONCLUSIONS These findings contribute to the continued research into natural substances with the potential for protecting cells against oxidative injury, with the consideration that RA and CGA are useful in the regeneration of damaged stem cells.
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Affiliation(s)
- J M M Andrade
- Laboratory of Pharmacognosy, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, 90.610-000, Porto Alegre, RS, Brazil
| | - N Maurmann
- Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, 90.610-000, Porto Alegre, RS, Brazil.,Post-graduate Program in Physiology, UFRGS, Avenida Sarmento Leite, 500/sala PPG Fisiologia, 90.050-170, Porto Alegre, RS, Brazil
| | - D V Lopes
- Laboratory of Pharmacognosy, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, 90.610-000, Porto Alegre, RS, Brazil
| | - D P Pereira
- Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, 90.610-000, Porto Alegre, RS, Brazil
| | - P Pranke
- Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, 90.610-000, Porto Alegre, RS, Brazil.,Post-graduate Program in Physiology, UFRGS, Avenida Sarmento Leite, 500/sala PPG Fisiologia, 90.050-170, Porto Alegre, RS, Brazil.,Stem Cell Research Institute, Rua dos Andradas, 1464/133, 90.020-010, Porto Alegre, RS, Brazil
| | - A T Henriques
- Laboratory of Pharmacognosy, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, 90.610-000, Porto Alegre, RS, Brazil
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Blando S, Anchesi I, Mazzon E, Gugliandolo A. Can a Scaffold Enriched with Mesenchymal Stem Cells Be a Good Treatment for Spinal Cord Injury? Int J Mol Sci 2022; 23:ijms23147545. [PMID: 35886890 PMCID: PMC9319719 DOI: 10.3390/ijms23147545] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 07/01/2022] [Accepted: 07/05/2022] [Indexed: 12/10/2022] Open
Abstract
Spinal cord injury (SCI) is a worldwide highly crippling disease that can lead to the loss of motor and sensory neurons. Among the most promising therapies, there are new techniques of tissue engineering based on stem cells that promote neuronal regeneration. Among the different types of stem cells, mesenchymal stem cells (MSCs) seem the most promising. Indeed, MSCs are able to release trophic factors and to differentiate into the cell types that can be found in the spinal cord. Currently, the most common procedure to insert cells in the lesion site is infusion. However, this causes a low rate of survival and engraftment in the lesion site. For these reasons, tissue engineering is focusing on bioresorbable scaffolds to help the cells to stay in situ. Scaffolds do not only have a passive role but become fundamental for the trophic support of cells and the promotion of neuroregeneration. More and more types of materials are being studied as scaffolds to decrease inflammation and increase the engraftment as well as the survival of the cells. Our review aims to highlight how the use of scaffolds made from biomaterials enriched with MSCs gives positive results in in vivo SCI models as well as the first evidence obtained in clinical trials.
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Nel S, Durandt C, Murdoch C, Pepper MS. Determinants of Dental Pulp Stem Cell Heterogeneity. J Endod 2022; 48:1232-1240. [PMID: 35809811 DOI: 10.1016/j.joen.2022.06.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 06/27/2022] [Accepted: 06/28/2022] [Indexed: 11/17/2022]
Abstract
INTRODUCTION The aim of this review is to provide a narrative review on the determinants of dental pulp stem cell (DPSC) heterogeneity that may affect the regenerative properties of these cells. METHODS PubMed, Scopus and Medline (Ovid) literature searches were done on human dental pulp stem cell (hDPSC) heterogeneity. The focus was on human dental pulp stem cells (hDPSCs) with a primary focus on DPSC heterogeneity. RESULTS DPSCs display significant heterogeneity as illustrated by the various subpopulations reported, including differences in proliferation and differentiation capabilities and the impact of various intrinsic and extrinsic factors. CONCLUSIONS The lack of consistent and reliable results in the clinical setting may be due to the heterogeneous nature of DPSC populations. Standardization in isolation techniques and in criteria to characterize DPSCs should lead to less variability in results reported and improve comparison of findings between studies. Single-cell RNA sequencing holds promise in elucidating DPSC heterogeneity and may contribute to the establishment of standardized techniques.
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Affiliation(s)
- Sulette Nel
- Department of Oral Pathology and Oral Biology, School of Dentistry, Faculty of Health Sciences, University of Pretoria, South Africa.
| | - Chrisna Durandt
- Institute for Cellular and Molecular Medicine (ICMM), Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, South Africa
| | - Candice Murdoch
- Institute for Cellular and Molecular Medicine (ICMM), Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, South Africa
| | - Michael S Pepper
- Institute for Cellular and Molecular Medicine (ICMM), Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, South Africa
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Moghanian A, Cecen B, Nafisi N, Miri Z, Rosenzweig DH, Miri AK. Review of Current Literature for Vascularized Biomaterials in Dental Repair. Biochem Eng J 2022. [DOI: 10.1016/j.bej.2022.108545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
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Different Sources of Mesenchymal Stem Cells for Tissue Regeneration: A Guide to Identifying the Most Favorable One in Orthopedics and Dentistry Applications. Int J Mol Sci 2022; 23:ijms23116356. [PMID: 35683035 PMCID: PMC9181542 DOI: 10.3390/ijms23116356] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 05/31/2022] [Accepted: 06/03/2022] [Indexed: 12/04/2022] Open
Abstract
The success of regenerative medicine in various clinical applications depends on the appropriate selection of the source of mesenchymal stem cells (MSCs). Indeed, the source conditions, the quality and quantity of MSCs, have an influence on the growth factors, cytokines, extracellular vesicles, and secrete bioactive factors of the regenerative milieu, thus influencing the clinical result. Thus, optimal source selection should harmonize this complex setting and ensure a well-personalized and effective treatment. Mesenchymal stem cells (MSCs) can be obtained from several sources, including bone marrow and adipose tissue, already used in orthopedic regenerative applications. In this sense, for bone, dental, and oral injuries, MSCs could provide an innovative and effective therapy. The present review aims to compare the properties (proliferation, migration, clonogenicity, angiogenic capacity, differentiation potential, and secretome) of MSCs derived from bone marrow, adipose tissue, and dental tissue to enable clinicians to select the best source of MSCs for their clinical application in bone and oral tissue regeneration to delineate new translational perspectives. A review of the literature was conducted using the search engines Web of Science, Pubmed, Scopus, and Google Scholar. An analysis of different publications showed that all sources compared (bone marrow mesenchymal stem cells (BM-MSCs), adipose tissue mesenchymal stem cells (AT-MSCs), and dental tissue mesenchymal stem cells (DT-MSCs)) are good options to promote proper migration and angiogenesis, and they turn out to be useful for gingival, dental pulp, bone, and periodontal regeneration. In particular, DT-MSCs have better proliferation rates and AT and G-MSC sources showed higher clonogenicity. MSCs from bone marrow, widely used in orthopedic regenerative medicine, are preferable for their differentiation ability. Considering all the properties among sources, BM-MSCs, AT-MSCs, and DT-MSCs present as potential candidates for oral and dental regeneration.
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Niu F, Xu J, Yan Y. Histone demethylase KDM5A regulates the functions of human periodontal ligament stem cells during periodontitis via the miR-495-3p/HOXC8 axis. Regen Ther 2022; 20:95-106. [PMID: 35509266 PMCID: PMC9046131 DOI: 10.1016/j.reth.2021.12.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 12/01/2021] [Accepted: 12/15/2021] [Indexed: 11/13/2022] Open
Affiliation(s)
- Fang Niu
- Department of Oral Implantology and Prosthodontics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450000, PR China
- Corresponding author. Department of Oral Implantology and Prosthodontics, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Erqi District, Zhengzhou, Henan Province, 450000, China.
| | - Jing Xu
- Department of Oral Orthodontics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450000, PR China
| | - Yujuan Yan
- Department of Oral Prosthodontics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450000, PR China
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Guo M, Liu F, Wang W, Liu Z, Zhu Z, Liu Y, Huang Z. Naringin Promotes Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells via Wnt/ β-Catenin. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:4505471. [PMID: 35677363 PMCID: PMC9168102 DOI: 10.1155/2022/4505471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 05/11/2022] [Accepted: 05/19/2022] [Indexed: 11/24/2022]
Abstract
Purpose This investigation intended to unravel the effect and mechanism of naringin on the proliferation and osteogenic differentiation of human dental pulp stem cells (hDPSCs). Methods hDPSCs were induced to differentiate, and the degree of cell differentiation was observed by alizarin red staining, Oil Red O staining, and Alcian blue staining. hDPSCs were treated with 0, 20, 40, and 80 μmol/L naringin for 48 h, respectively. The proliferation rate and chemotaxis of the cells were measured by MTT and transwell assay, alkaline phosphatase (ALP) activity and osteogenic differentiation degree by ALP staining and alizarin red staining, and gene expression of osteogenic markers by qRT-PCR. Additionally, western blot was performed to test the levels of Wnt/β-catenin signaling-related proteins in hDPSCs. Results The isolated hDPSCs with spindle-shaped morphology had good differentiation capability. Further experiments confirmed naringin-caused increases in the proliferation rate and migration ability of hDPSCs. In addition, compared with the control group, naringin-treated cells had strong ALP activity and ossification levels and higher expression of Runx2, OPN, DSPP, and DMP1. The western blot results showed that naringin significantly activated Wnt/β-catenin signaling in hDPSCs. Conclusion Taken together, naringin enhances the proliferation, migration, and osteogenesis of hDPSCs through stimulating Wnt/β-catenin signaling pathway.
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Affiliation(s)
- Meiling Guo
- Department of General Dentistry, The Affiliated Stomatological Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China
- The Key Laboratory of Oral Biomedicine, Nanchang City, Jiangxi Province 330006, China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang City, Jiangxi Province 330006, China
| | - Fen Liu
- The Key Laboratory of Oral Biomedicine, Nanchang City, Jiangxi Province 330006, China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang City, Jiangxi Province 330006, China
- Department of Orthodontics, The Affiliated Stomatological Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China
| | - Wenjuan Wang
- The Key Laboratory of Oral Biomedicine, Nanchang City, Jiangxi Province 330006, China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang City, Jiangxi Province 330006, China
- Department of Orthodontics, The Affiliated Stomatological Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China
| | - Zhirong Liu
- The Key Laboratory of Oral Biomedicine, Nanchang City, Jiangxi Province 330006, China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang City, Jiangxi Province 330006, China
- Department of Orthodontics, The Affiliated Stomatological Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China
| | - Zhipeng Zhu
- The Key Laboratory of Oral Biomedicine, Nanchang City, Jiangxi Province 330006, China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang City, Jiangxi Province 330006, China
- Department of Orthodontics, The Affiliated Stomatological Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China
| | - Yiyu Liu
- The Key Laboratory of Oral Biomedicine, Nanchang City, Jiangxi Province 330006, China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang City, Jiangxi Province 330006, China
- Department of Orthodontics, The Affiliated Stomatological Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China
| | - Zhen Huang
- The Key Laboratory of Oral Biomedicine, Nanchang City, Jiangxi Province 330006, China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang City, Jiangxi Province 330006, China
- Department of Orthodontics, The Affiliated Stomatological Hospital of Nanchang University, Nanchang City, Jiangxi Province 330006, China
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Abdi S, Javanmehr N, Ghasemi-Kasman M, Bali HY, Pirzadeh M. Stem Cell-based Therapeutic and Diagnostic Approaches in Alzheimer's Disease. Curr Neuropharmacol 2022; 20:1093-1115. [PMID: 34970956 PMCID: PMC9886816 DOI: 10.2174/1570159x20666211231090659] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 07/24/2021] [Accepted: 09/21/2021] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Alzheimer's disease (AD) is a neurodegenerative impairment mainly recognized by memory loss and cognitive deficits. However, the current therapies against AD are mostly limited to palliative medications, prompting researchers to investigate more efficient therapeutic approaches for AD, such as stem cell therapy. Recent evidence has proposed that extensive neuronal and synaptic loss and altered adult neurogenesis, which is perceived pivotal in terms of plasticity and network maintenance, occurs early in the course of AD, which exacerbates neuronal vulnerability to AD. Thus, regeneration and replenishing the depleted neuronal networks by strengthening the endogenous repair mechanisms or exogenous stem cells and their cargoes is a rational therapeutic approach. Currently, several stem cell-based therapies as well as stem cell products like exosomes, have shown promising results in the early diagnosis of AD. OBJECTIVE This review begins with a comparison between AD and normal aging pathophysiology and a discussion on open questions in the field. Next, summarizing the current stem cell-based therapeutic and diagnostic approaches, we declare the advantages and disadvantages of each method. Also, we comprehensively evaluate the human clinical trials of stem cell therapies for AD. METHODOLOGY Peer-reviewed reports were extracted through Embase, PubMed, and Google Scholar until 2021. RESULTS With several ongoing clinical trials, stem cells and their derivatives (e.g., exosomes) are an emerging and encouraging field in diagnosing and treating neurodegenerative diseases. Although stem cell therapies have been successful in animal models, numerous clinical trials in AD patients have yielded unpromising results, which we will further discuss.
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Affiliation(s)
- Sadaf Abdi
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Nima Javanmehr
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Maryam Ghasemi-Kasman
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran;,Neuroscience Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran,Address correspondence to this author at the Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, P.O. Box 4136747176, Babol, Iran; Tel/Fax: +98-11-32190557; E-mail:
| | | | - Marzieh Pirzadeh
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
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Chen Y, Zhang Z, Yang X, Liu A, Liu S, Feng J, Xuan K. Odontogenic MSC Heterogeneity: Challenges and Opportunities for Regenerative Medicine. Front Physiol 2022; 13:827470. [PMID: 35514352 PMCID: PMC9061943 DOI: 10.3389/fphys.2022.827470] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 03/30/2022] [Indexed: 01/09/2023] Open
Abstract
Cellular heterogeneity refers to the genetic and phenotypic differences among cells, which reflect their various fate choices, including viability, proliferation, self-renewal probability, and differentiation into different lineages. In recent years, research on the heterogeneity of mesenchymal stem cells has made some progress. Odontogenic mesenchymal stem cells share the characteristics of mesenchymal stem cells, namely, good accessibility, low immunogenicity and high stemness. In addition, they also exhibit the characteristics of vasculogenesis and neurogenesis, making them attractive for tissue engineering and regenerative medicine. However, the usage of mesenchymal stem cell subgroups differs in different diseases. Furthermore, because of the heterogeneity of odontogenic mesenchymal stem cells, their application in tissue regeneration and disease management is restricted. Findings related to the heterogeneity of odontogenic mesenchymal stem cells urgently need to be summarized, thus, we reviewed studies on odontogenic mesenchymal stem cells and their specific subpopulations, in order to provide indications for further research on the stem cell regenerative therapy.
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Affiliation(s)
- Yuan Chen
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Zhaoyichun Zhang
- School of Stomatology, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xiaoxue Yang
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Anqi Liu
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Shiyu Liu
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Jianying Feng
- School of Stomatology, Zhejiang Chinese Medical University, Hangzhou, China
| | - Kun Xuan
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China
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Hypoxia Induces DPSC Differentiation versus a Neurogenic Phenotype by the Paracrine Mechanism. Biomedicines 2022; 10:biomedicines10051056. [PMID: 35625792 PMCID: PMC9138575 DOI: 10.3390/biomedicines10051056] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 04/28/2022] [Accepted: 04/28/2022] [Indexed: 12/10/2022] Open
Abstract
As previously described by several authors, dental pulp stem cells (DPSCs), when adequately stimulated, may acquire a neuronal-like phenotype acting as a favorable source of stem cells in the generation of nerves. Besides, it is known that hypoxia conditioning is capable of stimulating cell differentiation as well as survival and self-renewal, and that multiple growth factors, including Epidermal Growth factor (EGF) and basic fibroblast growth factor (bFGF), are often involved in the induction of the neuronal differentiation of progenitor cells. In this work, we investigated the role of hypoxia in the commitment of DPSCs into a neuronal phenotype. These cells were conditioned with hypoxia (O2 1%) for 5 and 16 days; subsequently, we analyzed the proliferation rate and morphology, and tested the cells for neural and stem markers. Moreover, we verified the possible autocrine/paracrine role of DPSCs in the induction of neural differentiation by comparing the secretome profile of the hypoxic and normoxic conditioned media (CM). Our results showed that the hypoxia-mediated DPSC differentiation was time dependent. Moreover, conditioned media (CM derived from DPSCs stimulated by hypoxia were able, in turn, to induce the neural differentiation of SH-SY5Y neuroblastoma cells and undifferentiated DPSCs. In conclusion, under the herein-mentioned conditions, hypoxia seems to favor the differentiation of DPSCs into neuron-like cells. In this way, we confirm the potential clinical utility of differentiated neuronal DPSCs, and we also suggest the even greater potential of CM-derived-hypoxic DPSCs that could more readily be used in regenerative therapies.
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