Understanding the Immunological Mechanisms of Mesenchymal Stem Cells in Allogeneic Transplantation: From the Aspect of Major Histocompatibility Complex Class I

Wang, Yafei; Tian, Mengya; Wang, Fei; Heng, Boon Chin; Zhou, Jing; Cai, Zhijian; Liu, Hua

doi:10.1089/scd.2018.0256

Cited by 40 publications

(37 citation statements)

References 73 publications

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“…However, the present study did not observe any statistically signi cant difference between APDLSCs and YPDLSCs. As the secondary signaling molecules of T cell activation, these proteins are co-stimulatory molecules that play an important role in host immune responses and immunoregulation (31,32). Therefore, the results of the present study show that both YPDLSCs and APDLSCs express low immunogenicity, i.e., donor age does not affect the immunogenicity of PDLSCs.…”

Section: Discussionmentioning

confidence: 50%

The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells

Zhang

Wang

et al. 2020

Preprint

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Abstract Background: Periodontal ligament stem cells (PDLSCs) have many applications in the field of cytotherapy, tissue engineering, and regenerative medicine. However, the effect of age on the biological and immunological characteristics of PDLSCs remains unclear. Methods: In this study, we compared PDLSCs isolated from young and adult individuals. PDLSCs proliferation was analyzed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining, and apoptosis level was detected by Annexin V-PE/7-ADD staining. PDLSCs osteogenic/adipogenic/chondrogenic differentiation potentials were assessed by alkaline phosphatase (ALP), Alizarin Red, Oil Red O, Alcian Blue staining and related quantitative analysis. PDLSCs immunosuppressive capacity was determined by EdU and Annexin V-PE/7-ADD staining. To explore its underlying mechanism, microarray, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and western blot analyses were performed to detect differentially expressed genes and proteins in PDLSCs. Results: Our results demonstrated that with aging, the proliferation and osteogenic/adipogenic/chondrogenic differentiation potential of PDLSCs decreased, whereas apoptosis of PDLSCs increased. Moreover, the immunosuppressive ability of PDLSCs decreased with aging. Compared with PDLSCs from young subjects, analysis of mRNA expression revealed an upregulation of CCND3 and RC3H2, and a downregulation of Runx2, ALP, COL1A1, PPARγ2, CXCL12, FKBP1A, FKBP1B, NCSTN, P2RX7, PPP3CB, RIPK2, SLC11A1, and TP53 in those from adult individuals. Furthermore, protein expression levels of Runx2, ALP, COL1A1, and PPARγ2 in the adult group was decreased, whereas that of CCND3 increased. Conclusions: Taken together, aging influences biological and immunological characteristics of PDLSCs, and thus it is more appropriate to utilized PDLSCs from young individuals for tissue regeneration, post-aging treatment, and allotransplantation.

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Section: Discussionmentioning

confidence: 50%

The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells

Zhang

Wang

et al. 2020

Preprint

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“…However, the expression of HLA-DP, HLA-DQ, HLA-DR, CD80, and CD86 were not detected in the current study. As HLA-ABC is tightly related to immune rejection 7 , the engraftment efficiencies of the MSCs expanded with the different culture media were assessed. The data showed that the human MSCs expanded with PL had a lower engraftment efficiency than those expanded with CDM, with batch variations (Fig.…”

mentioning

confidence: 99%

“…MHC-I can induce CD8 + T cells to eliminate an allograft, and NK cells eliminate cells lacking MHC-I 7 , 8 . To further confirm that the variation in HLA-ABC expression contributes to the inconsistencies in the engraftment efficiency of MSCs expanded with PL, a cytolytic assay was conducted in vitro.…”

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confidence: 99%

“…Although the low immunogenicity of MSCs has been widely demonstrated and is accepted by most researchers, the immunogenic characteristics of MSCs should be reconsidered because immune rejection is one of the major issues that needs to be addressed in clinical studies 7 , 8 . It has been demonstrated that MHC I- and MHC II-mismatched allogenic MSCs can undergo immune-mediated rejection in mice 7 , 8 . Allogenic MSCs even induce immune memory, resulting in more rapid elimination of MSCs during a 2 nd MSCs transplantation 7 , 8 .…”

mentioning

confidence: 99%

“…It has been demonstrated that MHC I- and MHC II-mismatched allogenic MSCs can undergo immune-mediated rejection in mice 7 , 8 . Allogenic MSCs even induce immune memory, resulting in more rapid elimination of MSCs during a 2 nd MSCs transplantation 7 , 8 . Knocking out MHC-I, MHC-II or both can significantly suppress immune rejection and prolong graft survival 9 .…”

mentioning

confidence: 99%

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Improved therapeutic consistency and efficacy of mesenchymal stem cells expanded with chemically defined medium for systemic lupus erythematosus

Lian

et al. 2020

Cell Mol Immunol

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Allogeneic Mesenchymal Stromal Cells for Cartilage Regeneration: A Review of in Vitro Evaluation, Clinical Experience, and Translational Opportunities

Aldrich

Cui

Murphy

et al. 2021

Stem Cells Translational Medicine

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The paracrine signaling, immunogenic properties and possible applications of mesenchymal stromal cells (MSCs) for cartilage tissue engineering and regenerative medicine therapies have been investigated through numerous in vitro, animal model and clinical studies. The emerging knowledge largely supports the concept of MSCs as signaling and modulatory cells, exerting their influence through trophic and immune mediation rather than as a cell replacement therapy. The virtues of allogeneic cells as a ready-to-use product with well-defined characteristics of cell surface marker expression, proliferative ability, and differentiation capacity are well established. With clinical applications in mind, a greater focus on allogeneic cell sources is evident, and this review summarizes the latest published and upcoming clinical trials focused on cartilage regeneration adopting allogeneic and autologous cell sources. Moreover, we review the current understanding of immune modulatory mechanisms and the role of trophic factors in articular chondrocyte-MSC interactions that offer feasible targets for evaluating MSC activity in vivo within the intra-articular environment. Furthermore, bringing labeling and tracking techniques to the clinical setting, while inherently challenging, will be extremely informative as clinicians and researchers seek to bolster the case for the safety and efficacy of allogeneic MSCs. We therefore review multiple promising approaches for cell tracking and labeling, including both chimerism studies and imaging-based techniques, that have been widely explored in vitro and in animal models. Understanding the distribution and persistence of transplanted MSCs is necessary to fully realize their potential in cartilage regeneration techniques and tissue engineering applications.

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Understanding the Immunological Mechanisms of Mesenchymal Stem Cells in Allogeneic Transplantation: From the Aspect of Major Histocompatibility Complex Class I

Cited by 40 publications

References 73 publications

The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells

The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells

Improved therapeutic consistency and efficacy of mesenchymal stem cells expanded with chemically defined medium for systemic lupus erythematosus

Allogeneic Mesenchymal Stromal Cells for Cartilage Regeneration: A Review of in Vitro Evaluation, Clinical Experience, and Translational Opportunities

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