|
1
|
Zhang H, Liu D, Wu T, Chen C, Jiang J, Yang R. Exploring mesenchymal stem cell niches for regeneration. Sci Bull (Beijing) 2025; 70:1389-1393. [PMID: 40102087 DOI: 10.1016/j.scib.2025.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/20/2025]
Affiliation(s)
- Han Zhang
- Department of Orthodontics, NMPA Key Laboratory for Dental Materials National Engineering, Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing 100081, China
| | - Duo Liu
- Department of Orthodontics, NMPA Key Laboratory for Dental Materials National Engineering, Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing 100081, China
| | - Tong Wu
- Department of Orthodontics, NMPA Key Laboratory for Dental Materials National Engineering, Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing 100081, China
| | - Chider Chen
- Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104, USA
| | - Jiuhui Jiang
- Department of Orthodontics, NMPA Key Laboratory for Dental Materials National Engineering, Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing 100081, China.
| | - Ruili Yang
- Department of Orthodontics, NMPA Key Laboratory for Dental Materials National Engineering, Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing 100081, China.
| |
Collapse
|
|
2
|
Wang Y, She S, Li W, Zhu J, Li X, Yang F, Dai K. Inhibition of cGAS-STING pathway by stress granules after activation of M2 macrophages by human mesenchymal stem cells against drug induced liver injury. Mol Immunol 2024; 165:42-54. [PMID: 38150981 DOI: 10.1016/j.molimm.2023.12.005] [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: 07/08/2023] [Revised: 11/05/2023] [Accepted: 12/14/2023] [Indexed: 12/29/2023]
Abstract
OBJECTIVE Cells can produce stress granules (SGs) to protect itself from damage under stress. The cGAS-STING pathway is one of the important pattern recognition pathways in the natural immune system. This study was investigated whether human mesenchymal stem cells (hMSCs) could protect the liver by inducing M2 macrophages to produce SGs during acute drug induced liver injury (DILI) induced by acetaminophen (APAP). METHODS After intragastric administration of APAP in vivo to induce DILI mice model, hMSCs were injected into the tail vein. The co-culture system of hMSCs and M2 macrophages was established in vitro. It was further use SGs inhibitor anisomicin to intervene M2 macrophages. The liver histopathology, liver function, reactive oxygen species (ROS) level, apoptosis pathway, endoplasmic reticulum stress (ERS) level, SGs markers (G3BP1/TIA-1), cGAS-STING pathway, TNF-α, IL-6, IL-1β mRNA levels in liver tissue and M2 macrophages were observed. RESULTS In vivo experiments, it showed that hMSCs could alleviate liver injury, inhibite the level of ROS, apoptosis and ERS, protect liver function in DILI mice. The mount of M2 was increased in the liver. hMSCs could also induce the production of SGs, inhibit the cGAS-STING pathway and reduce TNF-α, IL-6, IL-1β mRNA expression. The results in vitro showed that hMSCs could induce the production of SGs in macrophages, inhibit the cGAS-STING pathway, promote the secretion of IL-4 and IL-13, and reduce TNF-α, IL-6, IL-1β mRNA level in cells. In the process of IL-4 inducing M2 macrophage activation, anisomycin could inhibit the production of SGs, activate the cGAS-STING pathway, and promote the inflammatory factor TNF-α, IL-6, IL-1β mRNA expression in cells. CONCLUSIONS HMSCs had a protective effect on acute DILI in mice induced by APAP. Its mechanism might involve in activating M2 type macrophages, promoting the production of SGs, inhibiting the cGAS-STING pathway, and reducing the expression of pro-inflammatory factors in macrophages, to reduce hepatocytes damage.
Collapse
Affiliation(s)
- Yao Wang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Sha She
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Wenyuan Li
- Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Jiling Zhu
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Xun Li
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Fan Yang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China.
| | - Kai Dai
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China.
| |
Collapse
|
|
3
|
Feng Z, Jin M, Liang J, Kang J, Yang H, Guo S, Sun X. Insight into the effect of biomaterials on osteogenic differentiation of mesenchymal stem cells: A review from a mitochondrial perspective. Acta Biomater 2023; 164:1-14. [PMID: 36972808 DOI: 10.1016/j.actbio.2023.03.032] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 03/02/2023] [Accepted: 03/21/2023] [Indexed: 03/29/2023]
Abstract
Bone damage may be triggered by a variety of factors, and the damaged area often requires a bone graft. Bone tissue engineering can serve as an alternative strategy for repairing large bone defects. Mesenchymal stem cells (MSCs), the progenitor cells of connective tissue, have become an important tool for tissue engineering due to their ability to differentiate into a variety of cell types. The precise regulation of the growth and differentiation of the stem cells used for bone regeneration significantly affects the efficiency of this type of tissue engineering. During the process of osteogenic induction, the dynamics and function of localized mitochondria are altered. These changes may also alter the microenvironment of the therapeutic stem cells and result in mitochondria transfer. Mitochondrial regulation not only affects the induction/rate of differentiation, but also influences its direction, determining the final identity of the differentiated cell. To date, bone tissue engineering research has mainly focused on the influence of biomaterials on phenotype and nuclear genotype, with few studies investigating the role of mitochondria. In this review, we provide a comprehensive summary of researches into the role of mitochondria in MSCs differentiation and critical analysis regarding smart biomaterials that are able to "programme" mitochondria modulation was proposed. STATEMENT OF SIGNIFICANCE: : • This review proposed the precise regulation of the growth and differentiation of the stem cells used to seed bone regeneration. • This review addressed the dynamics and function of localized mitochondria during the process of osteogenic induction and the effect of mitochondria on the microenvironment of stem cells. • This review summarized biomaterials which affect the induction/rate of differentiation, but also influences its direction, determining the final identity of the differentiated cell through the regulation of mitochondria.
Collapse
Affiliation(s)
- Ziyi Feng
- Department of Plastic Surgery, The First Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, 110002 Liaoning Province, China
| | - Meiqi Jin
- School of Intelligent Medicine, China Medical University, No.77, Puhe Road, Shenyang, 110122, Liaoning Province, China
| | - Junzhi Liang
- Center of Reproductive Medicine, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping, Shenyang, 110004 Liaoning Province, China
| | - Junning Kang
- Department of Neurosurgery, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping, Shenyang, 110004 Liaoning Province, China
| | - Huazhe Yang
- School of Intelligent Medicine, China Medical University, No.77, Puhe Road, Shenyang, 110122, Liaoning Province, China.
| | - Shu Guo
- Department of Plastic Surgery, The First Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, 110002 Liaoning Province, China.
| | - Xiaoting Sun
- School of Forensic Medicine, China Medical University, No.77, Puhe Road, Shenyang, 110122, Liaoning Province, China.
| |
Collapse
|
|
4
|
Tracy EP, Stielberg V, Rowe G, Benson D, Nunes SS, Hoying JB, Murfee WL, LeBlanc AJ. State of the field: cellular and exosomal therapeutic approaches in vascular regeneration. Am J Physiol Heart Circ Physiol 2022; 322:H647-H680. [PMID: 35179976 PMCID: PMC8957327 DOI: 10.1152/ajpheart.00674.2021] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 02/07/2022] [Accepted: 02/09/2022] [Indexed: 01/19/2023]
Abstract
Pathologies of the vasculature including the microvasculature are often complex in nature, leading to loss of physiological homeostatic regulation of patency and adequate perfusion to match tissue metabolic demands. Microvascular dysfunction is a key underlying element in the majority of pathologies of failing organs and tissues. Contributing pathological factors to this dysfunction include oxidative stress, mitochondrial dysfunction, endoplasmic reticular (ER) stress, endothelial dysfunction, loss of angiogenic potential and vascular density, and greater senescence and apoptosis. In many clinical settings, current pharmacologic strategies use a single or narrow targeted approach to address symptoms of pathology rather than a comprehensive and multifaceted approach to address their root cause. To address this, efforts have been heavily focused on cellular therapies and cell-free therapies (e.g., exosomes) that can tackle the multifaceted etiology of vascular and microvascular dysfunction. In this review, we discuss 1) the state of the field in terms of common therapeutic cell population isolation techniques, their unique characteristics, and their advantages and disadvantages, 2) common molecular mechanisms of cell therapies to restore vascularization and/or vascular function, 3) arguments for and against allogeneic versus autologous applications of cell therapies, 4) emerging strategies to optimize and enhance cell therapies through priming and preconditioning, and, finally, 5) emerging strategies to bolster therapeutic effect. Relevant and recent clinical and animal studies using cellular therapies to restore vascular function or pathologic tissue health by way of improved vascularization are highlighted throughout these sections.
Collapse
Affiliation(s)
- Evan Paul Tracy
- Cardiovascular Innovation Institute and the Department of Physiology, University of Louisville, Louisville, Kentucky
| | - Virginia Stielberg
- Cardiovascular Innovation Institute and the Department of Physiology, University of Louisville, Louisville, Kentucky
| | - Gabrielle Rowe
- Cardiovascular Innovation Institute and the Department of Physiology, University of Louisville, Louisville, Kentucky
| | - Daniel Benson
- Cardiovascular Innovation Institute and the Department of Physiology, University of Louisville, Louisville, Kentucky
- Department of Bioengineering, University of Louisville, Louisville, Kentucky
| | - Sara S Nunes
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
- Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
- Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Heart & Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, Ontario, Canada
| | - James B Hoying
- Advanced Solutions Life Sciences, Manchester, New Hampshire
| | - Walter Lee Murfee
- J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida
| | - Amanda Jo LeBlanc
- Cardiovascular Innovation Institute and the Department of Physiology, University of Louisville, Louisville, Kentucky
| |
Collapse
|
|
5
|
Potential of Bone-Marrow-Derived Mesenchymal Stem Cells for Maxillofacial and Periodontal Regeneration: A Narrative Review. Int J Dent 2021; 2021:4759492. [PMID: 34795761 PMCID: PMC8594991 DOI: 10.1155/2021/4759492] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 09/19/2021] [Accepted: 10/25/2021] [Indexed: 12/11/2022] Open
Abstract
Bone-marrow-derived mesenchymal stem cells (BM-MSCs) are one of the most widely studied postnatal stem cell populations and are considered to utilize more frequently in cell-based therapy and cancer. These types of stem cells can undergo multilineage differentiation including blood cells, cardiac cells, and osteogenic cells differentiation, thus providing an alternative source of mesenchymal stem cells (MSCs) for tissue engineering and personalized medicine. Despite the ability to reprogram human adult somatic cells to induced pluripotent stem cells (iPSCs) in culture which provided a great opportunity and opened the new door for establishing the in vitro disease modeling and generating an unlimited source for cell base therapy, using MSCs for regeneration purposes still have a great chance to cure diseases. In this review, we discuss the important issues in MSCs biology including the origin and functions of MSCs and their application for craniofacial and periodontal tissue regeneration, discuss the potential and clinical applications of this type of stem cells in differentiation to maxillofacial bone and cartilage in vitro, and address important future hopes and challenges in this field.
Collapse
|
|
6
|
Maxillofacial-Derived Mesenchymal Stem Cells: Characteristics and Progress in Tissue Regeneration. Stem Cells Int 2021; 2021:5516521. [PMID: 34426741 PMCID: PMC8379387 DOI: 10.1155/2021/5516521] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 07/06/2021] [Accepted: 07/15/2021] [Indexed: 12/11/2022] Open
Abstract
Maxillofacial-derived mesenchymal stem cells (MFSCs) are a particular collective type of mesenchymal stem cells (MSCs) that originate from the hard and soft tissue of the maxillofacial region. Recently, many types of MFSCs have been isolated and characterized. MFSCs have the common characteristics of being extremely accessible and amazingly multipotent and thus have become a promising stem cell resource in tissue regeneration. However, different MFSCs can give rise to different cell lineages, have different advantages in clinical use, and regulate the immune and inflammation microenvironment through paracrine mechanisms in different ways. Hence, in this review, we will concentrate on the updated new findings of all types of MFSCs in tissue regeneration and also introduce the recently discovered types of MFSCs. Important issues about proliferation and differentiation in vitro and in vivo, up-to-date clinical application, and paracrine effect of MFSCs in tissue regeneration will also be discussed. Our review may provide a better guide for the clinical use of MFSCs and further direction of research in MFSC regeneration medicine.
Collapse
|
|
7
|
Key Markers and Epigenetic Modifications of Dental-Derived Mesenchymal Stromal Cells. Stem Cells Int 2021; 2021:5521715. [PMID: 34046069 PMCID: PMC8128613 DOI: 10.1155/2021/5521715] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/08/2021] [Accepted: 04/17/2021] [Indexed: 12/13/2022] Open
Abstract
As a novel research hotspot in tissue regeneration, dental-derived mesenchymal stromal cells (MSCs) are famous for their accessibility, multipotent differentiation ability, and high proliferation. However, cellular heterogeneity is a major obstacle to the clinical application of dental-derived MSCs. Here, we reviewed the heterogeneity of dental-derived MSCs firstly and then discussed the key markers and epigenetic modifications related to the proliferation, differentiation, immunomodulation, and aging of dental-derived MSCs. These messages help to control the composition and function of dental-derived MSCs and thus accelerate the translation of cell therapy into clinical practice.
Collapse
|
|
8
|
Spatial Distributions, Characteristics, and Applications of Craniofacial Stem Cells. Stem Cells Int 2020; 2020:8868593. [PMID: 32908545 PMCID: PMC7475745 DOI: 10.1155/2020/8868593] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 07/29/2020] [Accepted: 08/01/2020] [Indexed: 02/05/2023] Open
Abstract
Stem cells play an irreplaceable role in the development, homeostasis, and regeneration of the craniofacial bone. Multiple populations of tissue-resident craniofacial skeletal stem cells have been identified in different stem cell niches, including the cranial periosteum, jawbone marrow, temporomandibular joint, cranial sutures, and periodontium. These cells exhibit self-renewal and multidirectional differentiation abilities. Here, we summarized the properties of craniofacial skeletal stem cells, based on their spatial distribution. Specifically, we focused on the in vivo genetic fate mapping of stem cells, by exploring specific stem cell markers and observing their lineage commitment in both the homeostatic and regenerative states. Finally, we discussed their application in regenerative medicine.
Collapse
|
|
9
|
Ding L, Ning HM, Li PL, Yan HM, Han DM, Zheng XL, Liu J, Zhu L, Xue M, Mao N, Guo ZK, Zhu H, Wang HX. Tumor necrosis factor α in aGVHD patients contributed to the impairment of recipient bone marrow MSC stemness and deficiency of their hematopoiesis-promotion capacity. Stem Cell Res Ther 2020; 11:119. [PMID: 32183881 PMCID: PMC7079531 DOI: 10.1186/s13287-020-01615-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 02/09/2020] [Accepted: 02/24/2020] [Indexed: 12/14/2022] Open
Abstract
Background Though accumulated evidence has demonstrated visceral organ involvement in acute graft-versus-host disease (aGVHD), how aGVHD influences the bone marrow (BM) niche and the reconstitution of hematopoiesis post-hematopoietic stem cell transplantation remains largely unknown. Methods In the current study, the cell morphology, immunophenotype, multi-differentiation capacity, self-renewal capacity, and hematopoiesis promotion of the MSCs from aGVHD and non-aGVHD patients were investigated. Additionally, the stemness and hematopoiesis-promoting property of healthy donor-derived MSCs were evaluated in the presence of BM supernatant from aGVHD patients. Mechanistically, antibodies targeting inflammatory cytokines involved in aGVHD were added into the MSC culture. Furthermore, a recombinant human tumor necrosis factor (TNF-α) receptor-Ig fusion protein (rhTNFR:Fc) was used to protect healthy donor-derived MSCs. Moreover, mRNA sequencing was performed to explore the underlying mechanisms. Results The aGVHD MSCs exhibited morphological and immunophenotypic characteristics that were similar to those of the non-aGVHD MSCs. However, the osteogenic and adipogenic activities of the aGVHD MSCs significantly decreased. Additionally, the colony formation capacity and the expression of self-renewal-related genes remarkably decreased in aGVHD MSCs. Further, the hematopoiesis-supporting capacity of aGVHD MSCs significantly reduced. The antibody neutralization results showed that TNF-α contributed to the impairment of MSC properties. Moreover, rhTNFR:Fc exhibited notable protective effects on MSCs in the aGVHD BM supernatants. The mRNA sequencing results indicated that the TNF-α pathway and the Toll-like receptor pathway may be activated by TNF-α. Conclusions Thus, our data demonstrate MSCs as cellular targets of aGVHD and suggest a potential role of TNF-α blockage in maintaining the BM niche of aGVHD patients.
Collapse
Affiliation(s)
- Li Ding
- Medical Center of Air Forces, PLA, Road Fucheng 30, Beijing, 100142, People's Republic of China.,Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, People's Republic of China
| | - Hong-Mei Ning
- The Fifth Medical Center of Chinese PLA General Hospital, East Street 8, Beijing, 100071, People's Republic of China
| | - Pei-Lin Li
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, People's Republic of China
| | - Hong-Min Yan
- Medical Center of Air Forces, PLA, Road Fucheng 30, Beijing, 100142, People's Republic of China
| | - Dong-Mei Han
- Medical Center of Air Forces, PLA, Road Fucheng 30, Beijing, 100142, People's Republic of China
| | - Xiao-Li Zheng
- Medical Center of Air Forces, PLA, Road Fucheng 30, Beijing, 100142, People's Republic of China
| | - Jing Liu
- Medical Center of Air Forces, PLA, Road Fucheng 30, Beijing, 100142, People's Republic of China
| | - Ling Zhu
- Medical Center of Air Forces, PLA, Road Fucheng 30, Beijing, 100142, People's Republic of China
| | - Mei Xue
- Medical Center of Air Forces, PLA, Road Fucheng 30, Beijing, 100142, People's Republic of China
| | - Ning Mao
- Beijing Institute of Basic Medical Sciences, Road Taiping 27, Beijing, 100850, People's Republic of China
| | - Zi-Kuan Guo
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, People's Republic of China.
| | - Heng Zhu
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, People's Republic of China.
| | - Heng-Xiang Wang
- Medical Center of Air Forces, PLA, Road Fucheng 30, Beijing, 100142, People's Republic of China.
| |
Collapse
|
|
10
|
Andrukhov O, Behm C, Blufstein A, Rausch-Fan X. Immunomodulatory properties of dental tissue-derived mesenchymal stem cells: Implication in disease and tissue regeneration. World J Stem Cells 2019; 11:604-617. [PMID: 31616538 PMCID: PMC6789188 DOI: 10.4252/wjsc.v11.i9.604] [Citation(s) in RCA: 132] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 04/24/2019] [Accepted: 08/27/2019] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are considered as an attractive tool for tissue regeneration and possess a strong immunomodulatory ability. Dental tissue-derived MSCs can be isolated from different sources, such as the dental pulp, periodontal ligament, deciduous teeth, apical papilla, dental follicles and gingiva. According to numerous in vitro studies, the effect of dental MSCs on immune cells might depend on several factors, such as the experimental setting, MSC tissue source and type of immune cell preparation. Most studies have shown that the immunomodulatory activity of dental MSCs is strongly upregulated by activated immune cells. MSCs exert mostly immunosuppressive effects, leading to the dampening of immune cell activation. Thus, the reciprocal interaction between dental MSCs and immune cells represents an elegant mechanism that potentially contributes to tissue homeostasis and inflammatory disease progression. Although the immunomodulatory potential of dental MSCs has been extensively investigated in vitro, its role in vivo remains obscure. A few studies have reported that the MSCs isolated from inflamed dental tissues have a compromised immunomodulatory ability. Moreover, the expression of some immunomodulatory proteins is enhanced in periodontal disease and even shows some correlation with disease severity. MSC-based immunomodulation may play an essential role in the regeneration of different dental tissues. Therefore, immunomodulation-based strategies may be a very promising tool in regenerative dentistry.
Collapse
Affiliation(s)
- Oleh Andrukhov
- Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna 1090, Austria.
| | - Christian Behm
- Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna 1090, Austria
| | - Alice Blufstein
- Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna 1090, Austria
| | - Xiaohui Rausch-Fan
- Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna 1090, Austria
| |
Collapse
|
|
11
|
Pilmane M, Sidhoma E, Akota I, Kazoka D. Characterization of Cytokines and Proliferation Marker Ki67 in Cleft Affected Lip Tissue. MEDICINA (KAUNAS, LITHUANIA) 2019; 55:E518. [PMID: 31443525 PMCID: PMC6780708 DOI: 10.3390/medicina55090518] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 08/07/2019] [Accepted: 08/19/2019] [Indexed: 12/29/2022]
Abstract
Background and objectives: Cleft lip palate takes the second place among all anomalies. The complex appearance of cytokines and proliferation markers has still not been clarified despite their possible crucial role in cleft tissue. Therefore, the aim of work was the detection of appearance of pro- and anti-inflammatory cytokines and proliferation marker Ki67, and their inter-correlations in cleft affected lip (CAL). Materials and Methods: The lip material was obtained from 16 children aged before primary dentition during plastic surgery. Control was obtained from 7 non-CAL oral tissue. Tissues were stained for IL-1, IL-4, IL-6, IL-8, IL-10 and Ki67 immunohistochemically. Non-parametric statistic, Mann-Whitney and Spearman's coefficient were used. Results: All cytokines positive cells were observed more into the epithelium. Statistically significant difference was seen between epithelial IL-1, IL-10, IL-8 and Ki67 positive cells and IL-10-, IL-4-containing connective tissue cells in comparison to the control. Strong positive correlation was detected in CAL epithelium between IL-10 and IL-8, IL-10 and IL-4, IL-10 and IL-1, IL-1 and IL-8, IL-1 and IL-4, IL-4 and IL-8, IL-8 and Ki67, IL-10 and Ki67, but moderate-in connective tissue between IL-1 and IL-10, IL-1 and IL-4. Conclusion: The CAL epithelium is the main source for the interleukins. Rich similar expression of IL-1 and IL-10 suggests the balance between pro-and anti-inflammatory tissue response on basis of dysregulated tissue homeostasis (increase of IL-8). The correlations between the different ILs -1, -4, -8, -10 in CAL epithelium seem to indicate the self-protection compensatory mechanism for intensification of local inflammatory-immune response without involvement of IL-6. The correlations between Ki67 and cytokines indicate the involvement of IL-8 and IL-10 in stimulation of cellular proliferation. IL-4 and IL-10 expression from CAL connective tissue simultaneously to IL-1, IL-4 and IL-10 inter-correlations there suggests the intensification of local immune response regulated probably by main pro-inflammatory cytokine-IL-1.
Collapse
Affiliation(s)
- Mara Pilmane
- Institute of Anatomy and Anthropology, Riga Stradins University , Kronvalda Boulevard 9, LV-1010 Riga, Latvia.
| | - Elga Sidhoma
- Institute of Anatomy and Anthropology, Riga Stradins University , Kronvalda Boulevard 9, LV-1010 Riga, Latvia
| | - Ilze Akota
- Institute of Stomatology, Riga Stradins University, Dzirciema Street 20, LV-1007 Riga, Latvia
| | - Dzintra Kazoka
- Institute of Anatomy and Anthropology, Riga Stradins University , Kronvalda Boulevard 9, LV-1010 Riga, Latvia
| |
Collapse
|
|
12
|
Kukolj T, Trivanović D, Mojsilović S, Okić Djordjević I, Obradović H, Krstić J, Jauković A, Bugarski D. IL-33 guides osteogenesis and increases proliferation and pluripotency marker expression in dental stem cells. Cell Prolif 2018; 52:e12533. [PMID: 30430681 PMCID: PMC6430470 DOI: 10.1111/cpr.12533] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 08/03/2018] [Accepted: 08/28/2018] [Indexed: 12/12/2022] Open
Abstract
Objectives Soluble IL‐33 (interleukin (IL)‐1‐like cytokine) acts as endogenous alarm signal (alarmin). Since alarmins, besides activating immune system, act to restore tissue homeostasis, we investigated whether IL‐33 exerts beneficial effects on oral stem cell pull. Materials and Methods Clonogenicity, proliferation, differentiation and senescence of stem cells derived from human periodontal ligament (PDLSCs) and dental pulp (DPSCs) were determined after in vitro exposure to IL‐33. Cellular changes were detected by flow cytometry, Western blot, immunocytochemistry and semiquantitative RT‐PCR. Results IL‐33 stimulated proliferation, clonogenicity and expression of pluripotency markers, OCT‐4, SOX‐2 and NANOG, but it inhibited ALP activity and mineralization in both PDLSCs and DPSCs. Higher Ki67 expression and reduced β‐galactosidase activity in IL‐33‐treated cells were demonstrated, whereas these trends were more conspicuous in osteogenic medium. However, after 7‐day IL‐33 pretreatment, differentiation capacity of IL‐33‐pretreated cells was retained, and increased ALP activity was observed in both cell types. Results showed that IL‐33 regulates NF‐κB and β‐catenin signalling, indicating the association of these molecules with changes observed in IL‐33‐treated PDLSCs and DPSCs, particularly their proliferation, pluripotency‐associated marker expression and osteogenesis. Conclusions IL‐33 treatment impairs osteogenesis of PDLSCs and DPSCs, while increases their clonogenicity, proliferation and pluripotency marker expression. After exposure to IL‐33, osteogenic capacity of cells stayed intact. NF‐κB and β‐catenin are implicated in the effects achieved by IL‐33 in PDLSCs and DPSCs.
Collapse
Affiliation(s)
- Tamara Kukolj
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Drenka Trivanović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Slavko Mojsilović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Ivana Okić Djordjević
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Hristina Obradović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Jelena Krstić
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Jauković
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Diana Bugarski
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| |
Collapse
|
|
13
|
Proksch S, Galler KM. Scaffold Materials and Dental Stem Cells in Dental Tissue Regeneration. ACTA ACUST UNITED AC 2018. [DOI: 10.1007/s40496-018-0197-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
|
|
14
|
Yang R, Liu Y, Yu T, Liu D, Shi S, Zhou Y, Zhou Y. Hydrogen sulfide maintains dental pulp stem cell function via TRPV1-mediated calcium influx. Cell Death Discov 2018; 4:1. [PMID: 30062050 PMCID: PMC6060166 DOI: 10.1038/s41420-018-0071-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2017] [Revised: 02/17/2018] [Accepted: 02/20/2018] [Indexed: 12/21/2022] Open
Abstract
Hydrogen sulfide (H2S), an endogenous gasotransmitter, mediated a variety of biological processes through multiple signaling pathways, and aberrant H2S metabolism has been associated with mesenchymal stem cell (MSC) dysfunction. Here we employed the small interfering RNA treatment for cystathionine β-synthase (CBS), cystathionine γ-lyase, the main enzymes to synthesize H2S, and CBS-knockout mice to analyze the effect of H2S on dental pulp homeostasis. We showed that H2S deficiency attenuated dental pulp stem cell (DPSC) osteogenic/dentinogenic differentiation in vitro and in vivo with enhanced cell proliferation. Mechanically, H2S facilitated the transient receptor potential action channel subfamily V member 1-mediated calcium (Ca2+) influx, which subsequently activated the β-catenin pathway. While H2S deficiency decreased Ca2+, resulting in glycogen synthase kinase-3β-mediated β-catenin degradation, which controls proliferation and differentiation of DPSCs. Consistently, H2S-deficient mice displayed disturbed pattern of dental pulp and less dentin formation. In this study, we identified a previously unknown mechanism by which H2S regulates DPSC lineage determination and dental pulp homeostasis.
Collapse
Affiliation(s)
- Ruili Yang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 100081 Beijing, China
- National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 100081 Beijing, China
- Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA
| | - Yi Liu
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, 100050 Beijing, China
| | - Tingting Yu
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 100081 Beijing, China
- National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 100081 Beijing, China
- Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA
| | - Dawei Liu
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 100081 Beijing, China
- National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 100081 Beijing, China
- Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA
| | - Songtao Shi
- Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA
| | - Yongsheng Zhou
- National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 100081 Beijing, China
- Department of Prosthodontics, Peking University School and Hospital of Stomatology, 100081 Beijing, China
| | - Yanheng Zhou
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 100081 Beijing, China
- National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 100081 Beijing, China
| |
Collapse
|
|
15
|
Reconstruction of Craniomaxillofacial Bone Defects Using Tissue-Engineering Strategies with Injectable and Non-Injectable Scaffolds. J Funct Biomater 2017; 8:jfb8040049. [PMID: 29156629 PMCID: PMC5748556 DOI: 10.3390/jfb8040049] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Revised: 11/09/2017] [Accepted: 11/14/2017] [Indexed: 02/06/2023] Open
Abstract
Engineering craniofacial bone tissues is challenging due to their complex structures. Current standard autografts and allografts have many drawbacks for craniofacial bone tissue reconstruction; including donor site morbidity and the ability to reinstate the aesthetic characteristics of the host tissue. To overcome these problems; tissue engineering and regenerative medicine strategies have been developed as a potential way to reconstruct damaged bone tissue. Different types of new biomaterials; including natural polymers; synthetic polymers and bioceramics; have emerged to treat these damaged craniofacial bone tissues in the form of injectable and non-injectable scaffolds; which are examined in this review. Injectable scaffolds can be considered a better approach to craniofacial tissue engineering as they can be inserted with minimally invasive surgery; thus protecting the aesthetic characteristics. In this review; we also focus on recent research innovations with different types of stem-cell sources harvested from oral tissue and growth factors used to develop craniofacial bone tissue-engineering strategies.
Collapse
|