Immunomodulatory Activity of Human Bone Marrow and Adipose-Derived Mesenchymal Stem Cells Prolongs Allogenic Skin Graft Survival in Nonhuman Primates.
Adipose
Allogenic
Bone Marrow
Immunomodulation
Mesenchymal Stem Cells
Journal
Cell journal
ISSN: 2228-5806
Titre abrégé: Cell J
Pays: Iran
ID NLM: 101566618
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
16
04
2019
accepted:
09
11
2019
entrez:
2
3
2021
pubmed:
3
3
2021
medline:
3
3
2021
Statut:
ppublish
Résumé
In the present study, we examined the tolerance-inducing effects of human adipose-derived mesenchymal stem cells (hAD-MSCs) and bone marrow-derived MSCs (hBM-MSCs) on a nonhuman primate model of skin transplantation. In this experimental study, allogenic and xenogeneic of immunomodulatory properties of human AD-MSCs and BM-MSCs were evaluated by mixed lymphocyte reaction (MLR) assays. Human MSCs were obtained from BM or AD tissues (from individuals of either sex with an age range of 35 to 65 years) and intravenously injected (2×106 MSCs/kg) after allogeneic skin grafting in a nonhuman primate model. The skin sections were evaluated by H and E staining for histopathological evaluations, particularly inflammation and rejection reaction of grafts after 96 hours of cell injection. At the mRNA and protein levels, cellular mediators of inflammation, such as CD4+IL-17+ (T helper 17; Th17) and CD4+INF-γ+ (T helper 1, Th1) cells, along with CD4+FoxP3+ cells (Treg), as the mediators of immunomodulation, were measured by RT-PCR and flow cytometry analyses. A significant Treg cells expansion was observed in MSCs-treated animals which reached the zenith at 24 hours and remained at a high concentration for 96 hours; however, Th1 and Th17 cells were significantly decreased. Our results showed that human MSCs significantly decrease Th1 and Th17 cell proliferation by decreasing interleukin-17 (IL-17) and interferon-γ (INF-γ) production and significantly increase Treg cell proliferation by increasing FoxP3 production. They also extend the allogenic skin graft survival in nonhuman primates. Histological evaluations showed no obvious presence of inflammatory cells or skin redness or even bulging after MSCs injection up to 96 hours, compared to the group without MSCs. There were no significant differences between hBM-MSCs and hAD-MSCs in terms of histopathological scores and inflammatory responses (P<0.05). It seems that MSCs could be regarded as a valuable immunomodulatory tool to reduce the use of immunosuppressive agents.
Identifiants
pubmed: 33650815
doi: 10.22074/cellj.2021.6895
pmc: PMC7944119
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1-13Informations de copyright
Copyright© by Royan Institute. All rights reserved.
Déclaration de conflit d'intérêts
There is no conflict of interest in this study.
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