Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis.
Aside from the well-established self-renewal and multipotent differentiation properties, mesenchymal stem cells exhibit both immunomodulatory and anti-inflammatory roles in several experimental autoimmune and inflammatory diseases. In this study, we isolated a new population of stem cells from human gingiva, a tissue source easily accessible from the oral cavity, namely, gingiva-derived mesenchymal stem cells (GMSCs), which exhibited clonogenicity, self-renewal, and multipotent differentiation capacities. Most importantly, GMSCs were capable of immunomodulatory functions, specifically suppressed peripheral blood lymphocyte proliferation, induced expression of a wide panel of immunosuppressive factors including IL-10, IDO, inducible NO synthase (iNOS), and cyclooxygenase 2 (COX-2) in response to the inflammatory cytokine, IFN-gamma. Cell-based therapy using systemic infusion of GMSCs in experimental colitis significantly ameliorated both clinical and histopathological severity of the colonic inflammation, restored the injured gastrointestinal mucosal tissues, reversed diarrhea and weight loss, and suppressed the overall disease activity in mice. The therapeutic effect of GMSCs was mediated, in part, by the suppression of inflammatory infiltrates and inflammatory cytokines/mediators and the increased infiltration of regulatory T cells and the expression of anti-inflammatory cytokine IL-10 at the colonic sites. Taken together, GMSCs can function as an immunomodulatory and anti-inflammatory component of the immune system in vivo and is a promising cell source for cell-based treatment in experimental inflammatory diseases.
Zhang
Qunzhou
Q
Center for Craniofacial Molecular Biology, University of Southern California, School of Dentistry, Los Angeles, CA 90033, USA.
Shi
Shihong
S
Liu
Yi
Y
Uyanne
Jettie
J
Shi
Yufang
Y
Shi
Songtao
S
Le
Anh D
AD
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D003092:Colitis / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D005881:Gingiva / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation / Q000502:physiology*; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011897:Random Allocation
D018836:Inflammation Mediators