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Rahnama Sisakht A, Tavasouli Z, Negahi A, Hosseini SA, Satarzadeh M. Dental pulp stem cells regenerate neural tissue in degenerative disorders and stroke rehabilitation: A scope systematic review. Heliyon 2024; 10:e35080. [PMID: 39166055 PMCID: PMC11334686 DOI: 10.1016/j.heliyon.2024.e35080] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 07/12/2024] [Accepted: 07/22/2024] [Indexed: 08/22/2024] Open
Abstract
Background Dental Pulp Stem Cells (DPSCs) possess a remarkable ability for tissue differentiation, making them highly efficient in tissue regeneration and inflammation regulation. This systematic study proposes to find an answer to the question, "Do DPSCs have the ability to regenerate and rehabilitate nerve tissue?" Methods This systematic review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, and the principle of non-bias was respected. All the articles from 2014 to 2024 were extracted from the Web of Science, PubMed, and Scopus databases. This study extracted the antigens and pro-inflammatory factors associated with DPSCs' involvement and how they affect the CNS's neural tissue regeneration. Results Two persons of researchers searched the database. After screening the full texts, they included 11 articles in their study. DPSCs control the following antigens: CD73, CD34, CD90, CD105, CD14, CD45, CD19Oct-4, CD73, CD31, CD34CD29CD44. Even though hematopoietic markers did not change much, OCT-4 and CD-73 were increased by DPSCs. DPSC-derived exosomes suppressed the expression of IL-6, IL-1β, TNF-α, and TGF, key mediators of nerve tissue inflammation. Additionally, DPSCs show high Vascular Endothelial Growth Factor (VEGF) expression in mice brain tissue cultures. DPSCs reduce Subarachnoid Hemorrhage (SAH), a condition in which blood collects in the subarachnoid space and causes ischemia. Discussion DPSCs showed the ability to regenerate nerve tissue and brain ganglia, stimulating angiogenesis by expressing cell markers and controlling growth factors in mice, and high therapeutic potential in neurodegenerative disorders. The present study invites further research in neurological disorders, specifically strokes, to prescribe these stem cells to the human population.
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Affiliation(s)
| | - Zahra Tavasouli
- Ghaemieh Health Care Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Ahmad Negahi
- School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
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Liu K, Sakai K, Watanabe J, Dong J, Maruyama H, Li X, Hibi H. Conditioned medium of human mesenchymal stem cells affects stem cell senescence in osteoporosis. Biochem Biophys Res Commun 2024; 711:149858. [PMID: 38621345 DOI: 10.1016/j.bbrc.2024.149858] [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: 11/21/2023] [Revised: 02/26/2024] [Accepted: 03/27/2024] [Indexed: 04/17/2024]
Abstract
Systemic transplantation of mesenchymal stem cells (MSCs) and conditioned medium derived from MSCs have been reported to recover bone loss in animal models of osteoporosis; however, the underlying mechanisms remain unclear. We recently reported that extracellular vesicles released from human mesenchymal stem cells (hMSCs) prevent senescence of stem cells in bisphosphonate-related osteonecrosis of the jaw model. In this study, we aimed to compare the effects of conditioned medium (hMSCs-CM) from early and late passage hMSCs on cellular senescence and to verify the benefits of CM from early passage hMSCs in mitigating the progression of osteoporosis through the prevention of cellular senescence. We investigated the distinct endocrine effects of early (P5) and late (P17) passage hMSCs in vitro, as well as the preventive benefits of early passage hMSCs-CM in osteoporosis model triggered by ovariectomy. Our results indicate that long-term cultured hMSCs contributed to the progression of inflammatory transcriptional programs in P5 hMSCs, ultimately impairing their functionality and enhancing senescence-related characteristics. Conversely, early passage hMSCs reversed these alterations. Moreover, early passage hMSCs-CM infused intravenously in a postmenopausal osteoporosis mouse model suppressed bone degeneration and prevented osteoporosis by reducing ovariectomy-induced senescence in bone marrow MSCs and reducing the expression of senescence-associated secretory phenotype-related cytokines. Our findings highlight the high translational value of early passage hMSCs-CM in antiaging intervention and osteoporosis prevention.
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Affiliation(s)
- Kehong Liu
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
| | - Kiyoshi Sakai
- Department of Oral and Maxillofacial Surgery, Nagoya University Hospital, Nagoya, Aichi, Japan.
| | - Junna Watanabe
- Department of Oral and Maxillofacial Surgery, Nagoya University Hospital, Nagoya, Aichi, Japan
| | - Jiao Dong
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; Lung Bioengineering and Regeneration, Department of Experimental Medical Sciences, Faculty of Medicine, Lund University, Lund, Sweden
| | - Hiroshi Maruyama
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
| | - Xinheng Li
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
| | - Hideharu Hibi
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; Department of Oral and Maxillofacial Surgery, Nagoya University Hospital, Nagoya, Aichi, Japan
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陈 沐, 商 正, 程 懿, 李 可, 段 飞, 胡 雯. [Examination of the Thermal Stability and Swallowing Safety of a Self-Developed Enteral Nutrition Thickening Agent]. SICHUAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF SICHUAN UNIVERSITY. MEDICAL SCIENCE EDITION 2024; 55:769-776. [PMID: 38948293 PMCID: PMC11211772 DOI: 10.12182/20240560203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Indexed: 07/02/2024]
Abstract
Objective To experimentally validate the effects of a self-developed heat-stable thickening agent on the textual characteristics of enteral nutrition solutions of standard concentration and its applicability in improving dysphagia. Methods A gradient of different doses of the self-developed thickening agent (1.0 g, 1.5 g, 2.0 g, 2.5 g, and3.0 g) and three commonly used commercial thickeners were mixed with 23.391 g of a complete nutrition formula powder dissolved in 85 mL of purified water to prepare 100 mL standard concentration nutrition solutions. The textual parameters (cohesiveness, viscosity, thickness, and hardness) of these nutrition solutions were measured using a texture analyzer at various temperature gradients (20 ℃, 40 ℃, 60 ℃, and 80 ℃) to compare their thermal stability. A dysphagia rat model was created via epiglottectomy to explore the effects of the thickener on lung tissue damage scores and levels of inflammatory markers. The rats were divided into a test intervention group, a positive control group, a negative control group, and a blank control group (no surgery and normal feeding after fasting for one day), with 15 rats in each group. After fasting for one day post-surgery, the test intervention group was fed with the standard concentration nutrition solution thickened with the self-developed thickener, while the positive control group was given a standard concentration nutrition solution thickened with product 3, and the negative control group was fed a normal diet. All groups were fed for two weeks with food dyed with food-grade green dye. General conditions, body mass, and food intake were observed and recorded. After two weeks, abdominal aorta blood was collected, and heart, liver, spleen, lung, and kidney tissues were harvested and weighed to calculate the lung tissue organ coefficient. The organ conditions were evaluated using routine H&E staining, and lung damage was semi-quantitatively analyzed based on the Mikawa scoring criteria. Blood supernatants were collected to measure the total serum protein and albumin levels to determine the nutritional status of the rats. The expression of IL-6 and TNF-α genes in lung tissues was measured by RT-qPCR. IL-6 and TNF-α protein expression levels in lung tissues, lung tissue homogenate, and serum were measured by ELISA. The aspiration incidence rate was calculated. Results Within the dosage range of 1.0 g to 3.0 g, the self-developed thickener in the test samples exhibited superior thermal stability in cohesiveness compared to the three commercially available thickeners, with a statistically significant difference (P<0.01). The differences in the thermal stability of viscosity and hardness between the self-developed thickener and the three commercially available thickeners were not statistically significant. The viscosity stability was optimal for the self-developed thickener, followed by the commercially available thickeners 1 and 3, with thickeners 2 being the least stable, though the differences were not statistically significant (P>0.05). Product 1 showed the best thermal stability in thickness, followed by the self-developed thickener and product 2, while the product 3 exhibited the worst performance, with the difference being statistically significant (P<0.01). The self-developed thickener had the best thermal stability in hardness at temperatures ranging from 20℃ to 80 ℃, followed by products 1 and 2, with product 3 being the least stable. However, the differences were not statistically significant (P>0.05). Animal experiment results indicated that the body weight gain in the positive control group and the test intervention group was lower than that in the blank and negative control groups (P<0.01). The spleen coefficient of the intervention group was lower than that of the positive control group and the blank control group (P<0.01), while the heart, liver, and kidney coefficients were lower than those of the blank control group (P<0.01). The differences in the lung coefficient of the intervention group and those of the other three groups were no statistically significant. Levels of TP and ALB in the test intervention group, the positive control group, and the negative control group were all lower than those in the blank control group, with statistically significant differences (P<0.01). ELISA results showed that serum IL-6 levels in the blank and test intervention groups were lower than those in the negative and positive control groups (P<0.05), while the difference in the other indicators across the four groups were not statistically significant (P>0.05). There were no statistically significant differences among the four groups in terms of lung tissue damage pathology scores, or in the levels of IL-6 and TNF-α gene expression in lung tissues. The aspiration incidence rate was 0% in all groups. Conclusion The self-developed enteral nutrition thickening agent demonstrated excellent thermal stability and swallowing safety. Further research to explore its application in patients with dysphagia is warranted.
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Affiliation(s)
- 沐熙 陈
- 四川大学华西医院 临床营养科 四川大学华西临床医学院 （成都 610041）Department of Clinical Nutrition, West China Hospital/West China School of Medicine, Sichuan University, Chengdu 610041, China
| | - 正云 商
- 四川大学华西医院 临床营养科 四川大学华西临床医学院 （成都 610041）Department of Clinical Nutrition, West China Hospital/West China School of Medicine, Sichuan University, Chengdu 610041, China
| | - 懿 程
- 四川大学华西医院 临床营养科 四川大学华西临床医学院 （成都 610041）Department of Clinical Nutrition, West China Hospital/West China School of Medicine, Sichuan University, Chengdu 610041, China
| | - 可 李
- 四川大学华西医院 临床营养科 四川大学华西临床医学院 （成都 610041）Department of Clinical Nutrition, West China Hospital/West China School of Medicine, Sichuan University, Chengdu 610041, China
| | - 飞霞 段
- 四川大学华西医院 临床营养科 四川大学华西临床医学院 （成都 610041）Department of Clinical Nutrition, West China Hospital/West China School of Medicine, Sichuan University, Chengdu 610041, China
| | - 雯 胡
- 四川大学华西医院 临床营养科 四川大学华西临床医学院 （成都 610041）Department of Clinical Nutrition, West China Hospital/West China School of Medicine, Sichuan University, Chengdu 610041, China
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Santilli F, Fabrizi J, Santacroce C, Caissutti D, Spinello Z, Candelise N, Lancia L, Pulcini F, Delle Monache S, Mattei V. Analogies and Differences Between Dental Stem Cells: Focus on Secretome in Combination with Scaffolds in Neurological Disorders. Stem Cell Rev Rep 2024; 20:159-174. [PMID: 37962698 PMCID: PMC10799818 DOI: 10.1007/s12015-023-10652-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/02/2023] [Indexed: 11/15/2023]
Abstract
Mesenchymal stem cells (MSCs) are well known for their beneficial effects, differentiation capacity and regenerative potential. Dental-derived MSCs (DSCs) are more easily accessible and have a non-invasive isolation method rather than MSCs isolated from other sources (umbilical cord, bone marrow, and adipose tissue). In addition, DSCs appear to have a relevant neuro-regenerative potential due to their neural crest origin. However, it is now known that the beneficial effects of MSCs depend, at least in part, on their secretome, referring to all the bioactive molecules (neurotrophic factors) released in the conditioned medium (CM) or in the extracellular vesicles (EVs) in particular exosomes (Exos). In this review, we described the similarities and differences between various DSCs. Our focus was on the secretome of DSCs and their applications in cell therapy for neurological disorders. For neuro-regenerative purposes, the secretome of different DSCs has been tested. Among these, the secretome of dental pulp stem cells and stem cells from human exfoliated deciduous teeth have been the most widely studied. Both CM and Exos obtained from DSCs have been shown to promote neurite outgrowth and neuroprotective effects as well as their combination with scaffold materials (to improve their functional integration in the tissue). For these reasons, the secretome obtained from DSCs in combination with scaffold materials may represent a promising tissue engineering approach for neuroprotective and neuro-regenerative treatments.
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Affiliation(s)
- Francesca Santilli
- Biomedicine and Advanced Technologies Rieti Center, "Sabina Universitas", Via A.M. Ricci 35/A, 02100, Rieti, Italy
| | - Jessica Fabrizi
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Costantino Santacroce
- Biomedicine and Advanced Technologies Rieti Center, "Sabina Universitas", Via A.M. Ricci 35/A, 02100, Rieti, Italy
| | - Daniela Caissutti
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Zaira Spinello
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Niccolò Candelise
- National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 29900161, Rome, Italy
| | - Loreto Lancia
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy
| | - Fanny Pulcini
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy
| | - Simona Delle Monache
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy.
| | - Vincenzo Mattei
- Dipartimento di Scienze della Vita, della Salute e delle Professioni Sanitarie, Link Campus University, Via del Casale di San Pio V 44, 00165, Rome, Italy.
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Bastidas JG, Maurmann N, Scholl JN, Weber AF, Silveira RP, Figueiró F, Stimamiglio MA, Marcon B, Correa A, Pranke P. Secretome of stem cells from human exfoliated deciduous teeth (SHED) and its extracellular vesicles improves keratinocytes migration, viability, and attenuation of H 2 O 2 -induced cytotoxicity. Wound Repair Regen 2023; 31:827-841. [PMID: 38038971 DOI: 10.1111/wrr.13131] [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: 03/21/2023] [Revised: 09/14/2023] [Accepted: 11/10/2023] [Indexed: 12/02/2023]
Abstract
Therapies for wound healing using the secretome and extracellular vesicles (EVs) of mesenchymal stem/stromal cells have been shown to be successful in preclinical studies. This study aimed to characterise the protein content of the secretome from stem cells from human exfoliated deciduous teeth (SHED) and analyse the in vitro effects of SHED-conditioned medium (SHED-CM) and SHED extracellular vesicles (SHED-EVs) on keratinocytes. EVs were isolated and characterised. The keratinocyte viability and migration of cells treated with SHED-EVs and conditioned medium (CM) were evaluated. An HaCaT apoptosis model induced by H2 O2 in vitro was performed with H2 O2 followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and live/dead assays. Finally, the expression of vascular endothelial growth factor (VEGF) in keratinocytes treated with secretome and EVs was evaluated by immunofluorescence staining and confirmed with RT-qPCR. SHED-EVs revealed a cup-shaped morphology with expression of the classical markers for exosomes CD9 and CD63, and a diameter of 181 ± 87 nm. The internalisation of EVs by HaCaT cells was confirmed by fluorescence microscopy. Proteomic analysis identified that SHED-CM is enriched with proteins related to stress response and development, including cytokines (CXCL8, IL-6, CSF1, CCL2) and growth factors (IGF2, MYDGF, PDGF). The results also indicated that 50% CM and 0.4-0.6 μg/mL EVs were similarly efficient for improving keratinocyte viability, migration, and attenuation of H2 O2 -induced cytotoxicity. Additionally, expression of VEGF on keratinocytes increased when treated with SHED secretome and EVs. Furthermore, VEGF gene expression in keratinocytes increased significantly when treated with SHED secretome and EVs. Both SHED-CM and SHED-EVs may therefore be promising therapeutic tools for accelerating re-epithelialization in wound healing.
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Affiliation(s)
- Juliana Girón Bastidas
- Hematology & Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Post Graduate Program in Biological Sciences: Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Natasha Maurmann
- Hematology & Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Post Graduate Program in Biological Sciences: Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Juliete Nathali Scholl
- Post Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Augusto Ferreira Weber
- Post Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Raíssa Padilha Silveira
- Hematology & Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Fabricio Figueiró
- Post Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Biochemistry Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Marco Augusto Stimamiglio
- Stem Cells Basic Biology Laboratory, Instituto Carlos Chagas, FIOCRUZ/PR, Rua Professor Algacyr Munhoz Mader, Curitiba, Paraná, Brazil
| | - Bruna Marcon
- Stem Cells Basic Biology Laboratory, Instituto Carlos Chagas, FIOCRUZ/PR, Rua Professor Algacyr Munhoz Mader, Curitiba, Paraná, Brazil
| | - Alejandro Correa
- Stem Cells Basic Biology Laboratory, Instituto Carlos Chagas, FIOCRUZ/PR, Rua Professor Algacyr Munhoz Mader, Curitiba, Paraná, Brazil
| | - Patricia Pranke
- Hematology & Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Post Graduate Program in Biological Sciences: Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Stem Cell Research Institute (Instituto de Pesquisa com Células-tronco), Porto Alegre, Rio Grande do Sul, Brazil
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Fujii Y, Hatori A, Chikazu D, Ogasawara T. Application of Dental Pulp Stem Cells for Bone and Neural Tissue Regeneration in Oral and Maxillofacial Region. Stem Cells Int 2023; 2023:2026572. [PMID: 37035445 PMCID: PMC10076122 DOI: 10.1155/2023/2026572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 10/21/2022] [Accepted: 03/18/2023] [Indexed: 03/31/2023] Open
Abstract
In the oral and maxillofacial region, the treatment of severe bone defects, caused by fractures, cancers, congenital abnormalities, etc., remains a great challenge. In addition, neurological disorders are frequently accompanied by these bone defects or the treatments for them. Therefore, novel bone regenerative techniques and methods to repair nerve injury are eagerly sought. Among them, strategies using dental pulp stem cells (DPSCs) are promising options. Human DPSCs can be collected easily from extracted teeth and are now considered a type of mesenchymal stem cell with higher clonogenic and proliferative potential. DPSCs have been getting attention as a cell source for bone and nerve regeneration. In this article, we reviewed the latest studies on osteogenic or neural differentiation of DPSCs as well as bone or neural regeneration methods using DPSCs and discussed the potential of DPSCs for bone and nerve tissue regeneration.
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Song WP, Jin LY, Zhu MD, Wang H, Xia DS. Clinical trials using dental stem cells: 2022 update. World J Stem Cells 2023; 15:31-51. [PMID: 37007456 PMCID: PMC10052340 DOI: 10.4252/wjsc.v15.i3.31] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/20/2023] [Accepted: 03/08/2023] [Indexed: 03/23/2023] Open
Abstract
For nearly 20 years, dental stem cells (DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth and exfoliated deciduous teeth, periodontal ligaments, dental follicles, and gingival and apical papilla. They have several properties (such as self-renewal, multidirectional differentiation, and immunomodulation) and exhibit enormous potential for clinical applications. To date, many clinical articles and clinical trials using DSCs have reported the treatment of pulpitis, periapical lesions, periodontitis, cleft lip and palate, acute ischemic stroke, and so on, and DSC-based therapies obtained satisfactory effects in most clinical trials. In these studies, no adverse events were reported, which suggested the safety of DSC-based therapy. In this review, we outline the characteristics of DSCs and summarize clinical trials and their safety as DSC-based therapies. Meanwhile, we also present the current limitations and perspectives of DSC-based therapy (such as harvesting DSCs from inflamed tissue, applying DSC-conditioned medium/DSC-derived extracellular vesicles, and expanding-free strategies) to provide a theoretical basis for their clinical applications.
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Affiliation(s)
- Wen-Peng Song
- Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Lu-Yuan Jin
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
| | - Meng-Di Zhu
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
| | - Hao Wang
- Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Deng-Sheng Xia
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China.
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Mansouri E, Orazizadeh M, Mard SA, Gorji AV, Rashno M, Fakhredini F. Therapeutic Effect of Kidney Tubular Cells-Derived Conditioned Medium on the Expression of MicroRNA-377, MicroRNA-29a, Aquapurin-1, Biochemical, and Histopathological Parameters Following Diabetic Nephropathy Injury in Rats. Adv Biomed Res 2022; 11:119. [PMID: 36798914 PMCID: PMC9926036 DOI: 10.4103/abr.abr_375_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 01/07/2022] [Accepted: 02/02/2022] [Indexed: 12/28/2022] Open
Abstract
Background Diabetic nephropathy (DN) is a critical complication of diabetes mellitus. This study evaluates whether administration of conditioned medium from kidney tubular cells (KTCs-CM) has the ability to be efficacious as an alternative to cell-based therapy for DN. Materials and Methods CM of rabbit kidney tubular cells (RK13; KTCs) has been collected and after centrifugation, filtered with 0.2 filters. Four groups of rats have been utilized, including control, DN, DN treated with CM, and sham group. After diabetes induction by streptozotocin (50 mg/kg body weight) in rats, 0.8 ml of the CM was injected to each rat three times per day for 3 consecutive days. Then, 24-h urine protein, blood urea nitrogen (BUN), and serum creatinine (Scr) have been measured through detection kits. The histopathological effects of CM on kidneys were evaluated by periodic acid-Schiff staining and the expression of microRNAs (miRNAs) 29a and 377 by using the real-time polymerase chain reaction. The expression of aquapurin-1 (AQP1) protein was also examined by Western blotting. Results Intravenous injections of KTCs-CM significantly reduced the urine volume, protein 24-h, BUN, and Scr, decreased the miRNA-377, and increased miRNA-29a and AQP1 in DN treated with CM rats. Conclusion KTCs-CM may have the potential to prevent kidney injury from diabetes by regulating the microRNAs related to DN and improving the expression of AQP1.
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Affiliation(s)
- Esrafil Mansouri
- Department of Anatomical Sciences, Faculty of Medicine, Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mahmoud Orazizadeh
- Department of Anatomical Sciences, Faculty of Medicine, Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyyed Ali Mard
- Physiology Research Center, Research Institute for Infectious Diseases of Digestive System, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Armita Valizadeh Gorji
- Bone Marrow Transplantation Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammad Rashno
- Immunology Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Fereshtesadat Fakhredini
- Department of Anatomical Sciences, Faculty of Medicine, Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran,Address for correspondence: Dr. Fereshtesadat Fakhredini, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. E-mail:
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Human Multipotent Mesenchymal Stromal Cell–Derived Extracellular Vesicles Enhance Neuroregeneration in a Rat Model of Sciatic Nerve Crush Injury. Int J Mol Sci 2022; 23:ijms23158583. [PMID: 35955732 PMCID: PMC9369448 DOI: 10.3390/ijms23158583] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/29/2022] [Accepted: 07/29/2022] [Indexed: 02/01/2023] Open
Abstract
Peripheral nerve injury remains a serious problem for medicine, with no effective method of treatment at the moment. The most prominent example of this problem is neonatal brachial plexus palsy, which results from the stretching of the brachial plexus nerves in the birth or perinatal period. Multipotent mesenchymal cells (MSCs) and the extracellular vesicles (EVs) they produce are known to have a marked neuroprotective effect in central nervous system injuries. We suggested that the use of MSCs-derived EVs may be an effective approach to the regeneration of peripheral nerves after injury. Sciatic nerve injury was modeled in rats via crushing, and then a gel containing MSCs–EVs was applied to the injured area. After 15 and 30 days, a histological, physiological, and functional assessment of nerve, dorsal root ganglia (DRG), and innervated muscles’ recovery was performed. Transplantation of EVs to the area of sciatic nerve injury significantly reduced muscle atrophy as compared to the control group. Functional recovery of the innervated muscles, as measured by the extensor postural thrust test, was revealed 30 days after the surgery. We associate the obtained results with EVs-induced neuroprotective mechanisms, which were expressed in a decrease in apoptotic neuronal death and an increase in regeneration-associated proteins NF-200 and GAP-43, as well as in DRG and damaged nerve. We suggest that the therapeutic scheme we used is efficient for the treatment of acute peripheral nervous system injuries and can be transferred to the clinics. However, additional studies are required for a more detailed analysis of neuroprotection mechanisms.
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Chouaib B, Cuisinier F, Collart-Dutilleul PY. Dental stem cell-conditioned medium for tissue regeneration: Optimization of production and storage. World J Stem Cells 2022; 14:287-302. [PMID: 35662860 PMCID: PMC9136565 DOI: 10.4252/wjsc.v14.i4.287] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 05/19/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSC) effects on tissue regeneration are mainly mediated by their secreted substances (secretome), inducing their paracrine activity. This Conditioned medium (CM), including soluble factors (proteins, nucleic acids, lipids) and extracellular vesicles is emerging as a potential alternative to cell therapy. However, the manufacturing of CM suffers from variable procedures and protocols leading to varying results between studies. Besides, there is no well-defined optimized procedure targeting specific applications in regenerative medicine. AIM To focus on conditioned medium produced from dental MSC (DMSC-CM), we reviewed the current parameters and manufacturing protocols, in order to propose a standardization and optimization of these manufacturing procedures. METHODS We have selected all publications investigating the effects of dental MSC secretome in in vitro and in vivo models of tissue regeneration, in accordance with the PRISMA guidelines. RESULTS A total of 351 results were identified. And based on the inclusion criteria described above, 118 unique articles were included in the systematic review. DMSC-CM production was considered at three stages: before CM recovery (cell sources for CM), during CM production (culture conditions) and after production (CM treatment). CONCLUSION No clear consensus could be recovered as evidence-based methods, but we were able to describe the most commonly used protocols: donors under 30 years of age, dental pulp stem cells and exfoliated deciduous tooth stem cells with cell passage between 1 and 5, at a confluence of 70% to 80%. CM were often collected during 48 h, and stored at -80 °C. It is important to point out that the preconditioning environment had a significant impact on DMSC-CM content and efficiency.
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Affiliation(s)
- Batoul Chouaib
- Laboratory Bioengineering and Nanosciences UR_UM104, University of Montpellier, Montpellier 34000, France
| | - Frédéric Cuisinier
- Laboratory Bioengineering and Nanosciences UR_UM104, University of Montpellier, Montpellier 34000, France
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11
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Su J, Ge X, Jiang N, Zhang Z, Wu X. Efficacy of Mesenchymal Stem Cells from Human Exfoliated DeciduousTeeth and their Derivatives in Inflammatory Diseases Therapy. Curr Stem Cell Res Ther 2022; 17:302-316. [PMID: 35440314 DOI: 10.2174/1574888x17666220417153309] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/01/2022] [Accepted: 02/28/2022] [Indexed: 11/22/2022]
Abstract
Mesenchymal stem cells derived from postnatal orofacial tissues can be readily isolated and possess diverse origins, for example, from surgically removed teeth or gingiva. These cells exhibit stem cell properties, strong potential for self-renewal, and show multi-lineage differentiation, and they have therefore been widely employed in stem cell therapy, tissue regeneration, and inflammatory diseases. Among them, stem cells from human exfoliated deciduous teeth [SHED] and their derivatives have manifested wide application in the treatment of diseases because of their outstanding advantages- including convenient access, easy storage, and less immune rejection. Numerous studies have shown that most diseases are closely associated with inflammation and that inflammatory diseases are extremely destructive, can lead to necrosis of organ parenchymal cells, and can deposit excessive extracellular ma- trix in the tissues. Inflammatory diseases are thus the principal causes of disability and death from many diseases worldwide. SHED and their derivatives not only exhibit the basic characteristics of stem cells but also exhibit some special properties of their own, particularly with regard to their great potential in inhib- iting inflammation and tissue regeneration. SHED therapy may provide a new direction for the treatment of inflammation and corresponding tissue defects. In this review, we critically analyze and summarize the latest findings on the behaviors and functions of SHED, serum‑free conditioned medium from SHED [SHED-CM], and extracellular vesicles, especially exosomes, from SHED [SHED-Exos], and discuss their roles and underlying mechanisms in the control of inflammatory diseases, thus further highlighting additional functions for SHED and their derivatives in future therapies.
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Affiliation(s)
| | - Xuejun Ge
- Shanxi Medical University School and Hospital of Stomatology & Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan 030001, China
| | | | - Ziqian Zhang
- Shanxi Medical University School and Hospital of Stomatology & Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan 030001, China
| | - Xiaowen Wu
- Shanxi Medical University School and Hospital of Stomatology & Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan 030001, China
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12
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Contreras E, Bolívar S, Navarro X, Udina E. New insights into peripheral nerve regeneration: The role of secretomes. Exp Neurol 2022; 354:114069. [DOI: 10.1016/j.expneurol.2022.114069] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 02/05/2022] [Accepted: 04/03/2022] [Indexed: 11/04/2022]
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13
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Guo R, Yu J. Multipotency and Immunomodulatory Benefits of Stem Cells From Human Exfoliated Deciduous Teeth. FRONTIERS IN DENTAL MEDICINE 2022. [DOI: 10.3389/fdmed.2022.805875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Stem cells derived from human exfoliated deciduous teeth (SHEDs) are considered a promising cell population for cell-based or cell-free therapy and tissue engineering because of their proliferative, multipotency and immunomodulator. Based on recent studies, we find that SHEDs show the superior ability of nerve regeneration in addition to the potential of osteogenesis, odontogenesis owing to their derivation from the neural crest. Besides, much evidence suggests that SHEDs have a paracrine effect and can function as immunomodulatory regents attributing to their capability of secreting cytokines and extracellular vesicles. Here, we review the characteristic of SHEDs, their multipotency to regenerate damaged tissues, specifically concentrating on bones or nerves, following the paracrine activity or immunomodulatory benefits of their potential for clinical application in regenerative medicine.
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14
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Li X, Guan Y, Li C, Zhang T, Meng F, Zhang J, Li J, Chen S, Wang Q, Wang Y, Peng J, Tang J. Immunomodulatory effects of mesenchymal stem cells in peripheral nerve injury. Stem Cell Res Ther 2022; 13:18. [PMID: 35033187 PMCID: PMC8760713 DOI: 10.1186/s13287-021-02690-2] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 12/18/2021] [Indexed: 12/14/2022] Open
Abstract
Various immune cells and cytokines are present in the aftermath of peripheral nerve injuries (PNI), and coordination of the local inflammatory response is of great significance for the recovery of PNI. Mesenchymal stem cells (MSCs) exhibit immunosuppressive and anti-inflammatory abilities which can accelerate tissue regeneration and attenuate inflammation, but the role of MSCs in the regulation of the local inflammatory microenvironment after PNI has not been widely studied. Here, we summarize the known interactions between MSCs, immune cells, and inflammatory cytokines following PNI with a focus on the immunosuppressive role of MSCs. We also discuss the immunomodulatory potential of MSC-derived extracellular vesicles as a new cell-free treatment for PNI.
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Affiliation(s)
- Xiangling Li
- The Fourth Medical Center of Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.,Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, People's Republic of China.,The School of Medicine, Jinzhou Medical University, Jinzhou, 121099, People's Republic of China
| | - Yanjun Guan
- Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, People's Republic of China
| | - Chaochao Li
- Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, People's Republic of China
| | - Tieyuan Zhang
- Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, People's Republic of China
| | - Fanqi Meng
- Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, People's Republic of China.,Department of Spine Surgery, Peking University People's Hospital, Beijing, 100044, People's Republic of China
| | - Jian Zhang
- Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, People's Republic of China
| | - Junyang Li
- Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, People's Republic of China.,The School of Medicine, Nankai University, Tianjin, 300071, People's Republic of China
| | - Shengfeng Chen
- Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, People's Republic of China
| | - Qi Wang
- The Fourth Medical Center of Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.,The School of Medicine, Jinzhou Medical University, Jinzhou, 121099, People's Republic of China
| | - Yi Wang
- Department of Stomatology, First Medical Center, Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
| | - Jiang Peng
- Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, People's Republic of China.
| | - Jinshu Tang
- The Fourth Medical Center of Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
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15
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Gugliandolo A, Mazzon E. Dental Mesenchymal Stem Cell Secretome: An Intriguing Approach for Neuroprotection and Neuroregeneration. Int J Mol Sci 2021; 23:ijms23010456. [PMID: 35008878 PMCID: PMC8745761 DOI: 10.3390/ijms23010456] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 12/28/2021] [Accepted: 12/28/2021] [Indexed: 12/12/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are known for their beneficial effects and regenerative potential. In particular, dental-derived MSCs have the advantage of easier accessibility and a non-invasive isolation method. Moreover, thanks to their neural crest origin, dental MSCs seem to have a more prominent neuroregenerative potential. Indeed, in basal conditions they also express neuronal markers. However, it is now well known that the beneficial actions of MSCs depend, at least in part, on their secretome, referring to all the bioactive molecules released in the conditioned medium (CM) or in extracellular vesicles (EVs). In this review we focus on the applications of the secretome derived from dental MSCs for neuroregeneration and neuroprotection. The secretomes of different dental MSCs have been tested for their effects for neuroregenerative purposes, and the secretomes of dental pulp stem cells and stem cells from human exfoliated deciduous teeth are the most studied. Both the CM and EVs obtained from dental MSCs showed that they are able to promote neurite outgrowth and neuroprotective effects. Interestingly, dental-derived MSC secretome showed stronger neuroregenerative and neuroprotective effects compared to that obtained from other MSC sources. For these reasons, the secretome obtained from dental MSCs may represent a promising approach for neuroprotective treatments.
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16
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Bar JK, Lis-Nawara A, Grelewski PG. Dental Pulp Stem Cell-Derived Secretome and Its Regenerative Potential. Int J Mol Sci 2021; 22:ijms222112018. [PMID: 34769446 PMCID: PMC8584775 DOI: 10.3390/ijms222112018] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 11/02/2021] [Accepted: 11/04/2021] [Indexed: 12/11/2022] Open
Abstract
The therapeutic potential of the dental pulp stem (DSC) cell-derived secretome, consisting of various biomolecules, is undergoing intense research. Despite promising in vitro and in vivo studies, most DSC secretome-based therapies have not been implemented in human medicine because the paracrine effect of the bioactive factors secreted by human dental pulp stem cells (hDPSCs) and human exfoliated deciduous teeth (SHEDs) is not completely understood. In this review, we outline the current data on the hDPSC- and SHED-derived secretome as a potential candidate in the regeneration of bone, cartilage, and nerve tissue. Published reports demonstrate that the dental MSC-derived secretome/conditional medium may be effective in treating neurodegenerative diseases, neural injuries, cartilage defects, and repairing bone by regulating neuroprotective, anti-inflammatory, antiapoptotic, and angiogenic processes through secretome paracrine mechanisms. Dental MSC-secretomes, similarly to the bone marrow MSC-secretome activate molecular and cellular mechanisms, which determine the effectiveness of cell-free therapy. Many reports emphasize that dental MSC-derived secretomes have potential application in tissue-regenerating therapy due to their multidirectional paracrine effect observed in the therapy of many different injured tissues.
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17
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Experimental Injury Rodent Models for Oropharyngeal Dysphagia. BIOLOGY 2021; 10:biology10050360. [PMID: 33922472 PMCID: PMC8146227 DOI: 10.3390/biology10050360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 04/20/2021] [Accepted: 04/21/2021] [Indexed: 11/16/2022]
Abstract
Oropharyngeal dysphagia is a disorder that can make swallowing difficult and reduce the quality of life. Recently, the number of patients with swallowing difficulty has been increasing; however, no comprehensive treatment for such patients has been developed. Various experimental animal models that mimic oropharyngeal dysphagia have been developed to identify appropriate treatments. This review aims to summarize the experimentally induced oropharyngeal dysphagia rodent models that can be used to provide a pathological basis for dysphagia. The selected studies were classified into those reporting dysphagia rodent models showing lingual paralysis by hypoglossal nerve injury, facial muscle paralysis by facial nerve injury, laryngeal paralysis by laryngeal and vagus nerve injury, and tongue dysfunction by irradiation of the head and neck regions. The animals used in each injury model, the injury method that induced dysphagia, the screening method for dysphagia, and the results are summarized. The use of appropriate animal models of dysphagia may provide adequate answers to biological questions. This review can help in selecting a dysphagia animal system tailored for the purpose of providing a possible solution to overcome dysphagia.
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18
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Villarroel V, Fagalde P, Reininger D. Potential therapeutic uses of intraoral mesenchymal stem cells in other tissues of the body: A review. J Clin Exp Dent 2021; 13:e259-e267. [PMID: 33680328 PMCID: PMC7920563 DOI: 10.4317/jced.56809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 08/10/2020] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND Over the last few years, there has been a great advance in regenerative medicine, with various studies that have observed the ability to repair or regenerate dysfunctional tissues with the patient's own cells, such as with mesenchymal cells. In this area, mesenchymal stem cells (MSCs) from the oral cavity have attracted attention because of their easy access and multiple cellular differentiations. Multiple studies have shown the various clinical applications at the intraoral level, especially at the level of bone regeneration, but the potential applications of oral MSC at a systemic level have been scarcely described. Objective: The objective of this review was to describe the potential therapeutic uses of intraoral MSCs in other tissues of the organism. MATERIAL AND METHODS A review of the literature between 2000 and 2019. Only included those studies done on animals or humans. RESULTS Twenty five articles were selected, all performed on animals. The donor site most used were the temporary teeth exfoliated from humans, representing 56% of the total articles, followed by the dental pulp with 28% of the total articles included. Transplantation of intraoral mesenchymal cells in animals with neural tissue illness was the most studied therapy. CONCLUSIONS Although obtaining MSC of intraoral origin has proven to be a good alternative in regenerative medicine, achieving therapeutic uses in bone tissue, nervous tissue, liver tissue, skin tissue, ocular tissue, reperfusion of tissues and in autoimmune diseases, there is a lack of clinical studies that allow its safe use in humans. Key words:Mesenchymal stem cells, stem cell transplantation, regenerative medicine, dental component.
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Affiliation(s)
| | | | - David Reininger
- DDS, PhD, Master in Oral Surgery and Implantology, Assistant Professor, Universidad Mayor, Santiago, Chile
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19
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Dental Tissue-Derived Human Mesenchymal Stem Cells and Their Potential in Therapeutic Application. Stem Cells Int 2020; 2020:8864572. [PMID: 32952572 PMCID: PMC7482010 DOI: 10.1155/2020/8864572] [Citation(s) in RCA: 76] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 07/15/2020] [Indexed: 02/05/2023] Open
Abstract
Human mesenchymal stem cells (hMSCs) are multipotent cells, which exhibit plastic adherence, express specific cell surface marker spectrum, and have multi-lineage differentiation potential. These cells can be obtained from multiple tissues. Dental tissue-derived hMSCs (dental MSCs) possess the ability to give rise to mesodermal lineage (osteocytes, adipocytes, and chondrocytes), ectodermal lineage (neurocytes), and endodermal lineages (hepatocytes). Dental MSCs were first isolated from dental pulp of the extracted third molar and till now they have been purified from various dental tissues, including pulp tissue of permanent teeth and exfoliated deciduous teeth, apical papilla, periodontal ligament, gingiva, dental follicle, tooth germ, and alveolar bone. Dental MSCs are not only easily accessible but are also expandable in vitro with relative genomic stability for a long period of time. Moreover, dental MSCs have exhibited immunomodulatory properties by secreting cytokines. Easy accessibility, multi-lineage differentiation potential, and immunomodulatory effects make dental MSCs distinct from the other hMSCs and an effective tool in stem cell-based therapy. Several preclinical studies and clinical trials have been performed using dental MSCs in the treatment of multiple ailments, ranging from dental diseases to nondental diseases. The present review has summarized dental MSC sources, multi-lineage differentiation capacities, immunomodulatory features, its potential in the treatment of diseases, and its application in both preclinical studies and clinical trials. The regenerative therapeutic strategies in dental medicine have also been discussed.
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20
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Chen T, Li Y, Ni W, Tang B, Wei Y, Li J, Yu J, Zhang L, Gao J, Zhou J, Zhang W, Xu H, Hu J. Human Neural Stem Cell-Conditioned Medium Inhibits Inflammation in Macrophages Via Sirt-1 Signaling Pathway In Vitro and Promotes Sciatic Nerve Injury Recovery in Rats. Stem Cells Dev 2020; 29:1084-1095. [PMID: 32560594 DOI: 10.1089/scd.2020.0020] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Chronic persistent inflammation is thought to impede axon regeneration and cause demyelinating disease also with neuropathic pain, leading to more severe dysfunction after peripheral nerve injury. Increasing evidence indicates that neural stem cells (NSCs) have immunomodulatory effects, and previous studies have shown that many of the beneficial effects attributed to stem cell therapy may exert their therapeutic effects through paracrine mechanisms. In this research, the repairing effect of NSC-conditioned medium (NSC-CM) on sciatic nerve injury and its mechanism of repair were further explored. The present research showed that NSC-CM promoted histopathological and functional recovery after crush injury in rats, and what counts is that NSC-CM inhibited the inflammation of sciatic nerve in the late stage of injury. NSC-CM significantly downregulated the infiltration of proinflammatory factors [tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-1β] as well as decreased the CD68 inflammatory macrophages infiltrating in the sciatic nerve. In addition, to study the effect of NSC-CM on the inflammatory state of macrophages in vitro, lipopolysaccharide (LPS) was used to induce the proinflammation of macrophages. The results showed that NSC-CM decreased the expression of macrophage proinflammatory-related proteins (IL-6, IL-1β, TNF-α, inducible nitric oxide synthase) induced by LPS. The activation of Sirt-1 signaling in macrophages effectively countered the proinflammation induced by LPS in the presence of NSC-CM. Using Sirt-1-specific inhibitor EX527 partially weakened the anti-inflammatory effect of NSC-CM. Altogether, this study demonstrated for the first time that NSC-CM promotes functional recovery after sciatic nerve crush injury in vivo and also inhibits the inflammation in activated macrophages by activating Sirt-1 signaling pathway in vitro.
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Affiliation(s)
- Tianyan Chen
- Jinagsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Yilei Li
- Jinagsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Wei Ni
- Jinagsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Bin Tang
- Jinagsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Yusheng Wei
- Jinagsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Jing Li
- Jinagsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Jiahong Yu
- Jinagsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Lei Zhang
- Jinagsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Jianyi Gao
- Jinagsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Jiqin Zhou
- Jinagsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Weining Zhang
- Jinagsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Hong Xu
- Department of Clinical Laboratory, Zhenjiang Centre for Disease Prevention and Control, Zhenjiang, China
| | - Jiabo Hu
- Jinagsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
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21
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Peripheral Nerve Regeneration in a Novel Rat Model of Dysphagia. Methods Mol Biol 2020. [PMID: 32474871 DOI: 10.1007/978-1-0716-0655-1_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register]
Abstract
The superior laryngeal nerve (SLN) is known to play an essential role in the laryngeal reflex and swallowing. Damage to the SLN causes difficulty swallowing, that is, dysphagia. We successfully developed a novel rat model of dysphagia by SLN injury, in which we could evaluate the neuroregenerative capacity of stem cell from human exfoliated deciduous teeth (SHED). The dysphagic rats exhibit weight loss and altered drinking patterns. Furthermore, SLN injury induces a delayed onset of the swallowing reflex and accumulation of laryngeal debris in the pharynx. This rat model was used to evaluate the systemic application of SHED-conditioned medium (SHED-CM) as a therapeutic candidate for dysphagia. We found that SHED-CM promoted functional recovery and significant axonal regeneration in SLNs through the polarization shift of macrophages from activated inflammatory macrophages (M1) to anti-inflammatory macrophages (M2) and angiogenesis. This chapter describes the establishment of SLN-injury induced dysphagia rat model and the preparation and application of SHED-CM.
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22
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Improvement of Impaired Motor Functions by Human Dental Exfoliated Deciduous Teeth Stem Cell-Derived Factors in a Rat Model of Parkinson's Disease. Int J Mol Sci 2020; 21:ijms21113807. [PMID: 32471263 PMCID: PMC7312764 DOI: 10.3390/ijms21113807] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 05/24/2020] [Accepted: 05/25/2020] [Indexed: 12/15/2022] Open
Abstract
Parkinson's disease (PD) is a long-term degenerative disease of the central nervous system (CNS) that primarily affects the motor system. So far there is no effective treatment for PD, only some drugs, surgery, and comprehensive treatment can alleviate the symptoms of PD. Stem cells derived from human exfoliated deciduous teeth (SHED), mesenchymal stem cells derived from dental pulp, may have promising potential in regenerative medicine. In this study, we examine the therapeutic effect of SHED-derived conditioned medium (SHED-CM) in a rotenone-induced PD rat model. Intravenous administration of SHED-CM generated by standardized procedures significantly improved the PD symptoms accompanied with increased tyrosine hydroxylase amounts in the striatum, and decreased α-synuclein levels in both the nigra and striatum, from rotenone-treated rats. In addition, this SHED-CM treatment decreased both Iba-1 and CD4 levels in these brain areas. Gene ontology analysis indicated that the biological process of genes affected by SHED-CM was primarily implicated in neurodevelopment and nerve regeneration. The major constituents of SHED-CM included insulin-like growth factor binding protein-6 (IGFBP-6), tissue inhibitor of metalloproteinase (TIMP)-2, TIMP-1, and transforming growth factor 1 (TGF-1). RNA-sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) revealed that these factors may ameliorate PD symptoms through modulating the cholinergic synapses, calcium signaling pathways, serotoninergic synapses, and axon guidance. In conclusion, our data indicate that SHED-CM contains active constituents that may have promising efficacy to alleviate PD.
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23
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Ko CS, Chen JH, Su WT. Stem Cells from Human Exfoliated Deciduous Teeth: A Concise Review. Curr Stem Cell Res Ther 2020; 15:61-76. [DOI: 10.2174/1574888x14666191018122109] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 07/08/2019] [Accepted: 08/29/2019] [Indexed: 02/08/2023]
Abstract
Stem Cells from Human Exfoliated Deciduous Teeth (SHED) originate from the embryonic
neural crest as ectodermal mesenchymal stem cells and are isolated from human deciduous teeth.
SHED expresses the same cell markers as Embryonic Stem Cells (ESCs), such as OCT4 and NANOG,
which make SHED to have a significant impact on clinical applications. SHED possess higher rates of
proliferation, higher telomerase activity, increased cell population doubling, form sphere-like clusters,
and possess immature and multi-differentiation capacity; such high plasticity makes SHED one of the
most popular sources of stem cells for biomedical engineering. In this review, we describe the isolation
and banking method, the current development of SHED in regenerative medicine and tissue engineering
in vitro and in vivo.
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Affiliation(s)
| | - Jen-Hao Chen
- School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wen-Ta Su
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan
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24
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El Moshy S, Radwan IA, Rady D, Abbass MMS, El-Rashidy AA, Sadek KM, Dörfer CE, Fawzy El-Sayed KM. Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications. Stem Cells Int 2020; 2020:7593402. [PMID: 32089709 PMCID: PMC7013327 DOI: 10.1155/2020/7593402] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Revised: 12/23/2019] [Accepted: 01/10/2020] [Indexed: 12/13/2022] Open
Abstract
Regenerative medicine literature has proposed mesenchymal stem/progenitor cell- (MSC-) mediated therapeutic approaches for their great potential in managing various diseases and tissue defects. Dental MSCs represent promising alternatives to nondental MSCs, owing to their ease of harvesting with minimally invasive procedures. Their mechanism of action has been attributed to their cell-to-cell contacts as well as to the paracrine effect of their secreted factors, namely, secretome. In this context, dental MSC-derived secretome/conditioned medium could represent a unique cell-free regenerative and therapeutic approach, with fascinating advantages over parent cells. This article reviews the application of different populations of dental MSC secretome/conditioned medium in in vitro and in vivo animal models, highlights their significant implementation in treating different tissue' diseases, and clarifies the significant bioactive molecules involved in their regenerative potential. The analysis of these recent studies clearly indicate that dental MSCs' secretome/conditioned medium could be effective in treating neural injuries, for dental tissue regeneration, in repairing bone defects, and in managing cardiovascular diseases, diabetes mellitus, hepatic regeneration, and skin injuries, through regulating anti-inflammatory, antiapoptotic, angiogenic, osteogenic, and neurogenic mediators.
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Affiliation(s)
- Sara El Moshy
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Israa Ahmed Radwan
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Dina Rady
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Marwa M. S. Abbass
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Aiah A. El-Rashidy
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Biomaterials Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Khadiga M. Sadek
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Biomaterials Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Christof E. Dörfer
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
| | - Karim M. Fawzy El-Sayed
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
- Oral Medicine and Periodontology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
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Man RC, Sulaiman N, Idrus RBH, Ariffin SHZ, Wahab RMA, Yazid MD. Insights into the Effects of the Dental Stem Cell Secretome on Nerve Regeneration: Towards Cell-Free Treatment. Stem Cells Int 2019; 2019:4596150. [PMID: 31772587 PMCID: PMC6855004 DOI: 10.1155/2019/4596150] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 08/28/2019] [Accepted: 09/16/2019] [Indexed: 12/11/2022] Open
Abstract
Cell-free treatment is emerging as an alternative to cell delivery to promote endogenous regeneration using cell-derived factors. The purpose of this article was to systematically review studies of the effects of the dental stem cell secretome on nerve regeneration. PubMed and Scopus databases were used where searched and related studies were selected. The primary search identified 36 articles with the utilized keywords; however, only 13 articles met the defined inclusion criteria. Eight out of thirteen articles included in vivo and in vitro studies. We classified the dental stem cell-derived secretome with its nerve regeneration potential. All studies demonstrated that dental stem cell-derived factors promote neurotrophic effects that can mechanistically stimulate nerve regeneration in neurodegenerative diseases and nerve injury. This data collection will enable researchers to gather information to create a precise formulation for future prescribed treatments.
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Affiliation(s)
- Rohaina Che Man
- Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia
| | - Nadiah Sulaiman
- Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia
| | - Ruszymah Bt Hj Idrus
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia
| | - Shahrul Hisham Zainal Ariffin
- Malaysia Genome Institute (MGI), National Institute of Biotechnology Malaysia (NIBM), Jalan Bangi, 43000 Bangi, Selangor, Malaysia
- Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Selangor 43600, Malaysia
| | - Rohaya Megat Abdul Wahab
- Department of Orthodontic, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia
| | - Muhammad Dain Yazid
- Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia
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