Mesenchymal Stem Cells Derived from Human Gingiva Are Capable of Immunomodulatory Functions and Ameliorate Inflammation-Related Tissue Destruction in Experimental Colitis

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Departmental Papers (Dental)
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MeSH: Adult
Animals
Cells
Cultured
Coculture Techniques
Colitis
Female
Gingiva
Humans
Immunomodulation
Inflammation Mediators
Male
Mesenchymal Stem Cells
Mice
Mice
Inbred C57BL
Mice
Nude
Random Allocation EMTREE drug terms: cyclooxygenase 2
gamma interferon
indoleamine 2
3 dioxygenase
inducible nitric oxide synthase
interleukin 10
autacoid EMTREE medical terms: animal experiment
animal model
article
cell differentiation
cell population
cell renewal
cell therapy
clonogenesis
colitis
controlled study
diarrhea
disease activity
disease severity
female
gastrointestinal mucosa
gingiva
histopathology
human
human cell
human tissue
immunomodulation
inflammation
inflammatory disease
inflammatory infiltrate
lymphocyte proliferation
male
mesenchymal stem cell
mouse
multipotent stem cell
nonhuman
priority journal
protein expression
regulatory T lymphocyte
upregulation
weight reduction
adult
animal
C57BL mouse
cell culture
coculture
colitis
cytology
immunology
immunomodulation
metabolism
nude mouse
physiology
randomization
Dentistry
Oral Biology and Oral Pathology
Periodontics and Periodontology
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Zheng, Qunzhou
Shi, Shihong
Liu, Yi
Uyanne, Jettie
Shi, Yufang
Shi, Songtao
Le, Anh D
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Abstract

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-γ. 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. Copyright © 2009 by The American Association of Immunologists, Inc.

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2009-12-15
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Journal of Immunology
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At the time of publication, author Qunzhou Zheng was affiliated with the University of Southern California, School of Dentistry. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania. At the time of publication, author Shihong Shi was affiliated with the University of Southern California, School of Dentistry. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania. At the time of publication, author Songtao Shi was affiliated with the University of Southern California, School of Dentistry. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania. At the time of publication, author Anh D. Le was affiliated with the University of Medicine and Dentistry of New Jersey. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.
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