Adoptive Transfer of Human Gingiva-derived Mesenchymal Stem Cells Ameliorates Collagen-induced Arthritis via Suppression of Th1 and Th17 Cells and Enhancement of Regulatory T Cell Differentiation
Penn collection
Degree type
Discipline
Subject
Animals
Antigens
CD
Apyrase
Arthritis
Experimental
Cell Differentiation
Female
Gingiva
GPI-Linked Proteins
Humans
Immunotherapy
Adoptive
Mesenchymal Stem Cell Transplantation
Mesenchymal Stromal Cells
Mice
Mice
Inbred DBA
Signal Transduction
T-Lymphocytes
Regulatory
Th1 Cells
Th17 Cells
5' nucleotidase
beta1 integrin
CD25 antibody
CD39 antigen
collagen type 2
endoglin
Freund adjuvant
gamma interferon
Hermes antigen
interleukin 10
interleukin 13
interleukin 17
interleukin 4
interleukin 5
lymphocyte antibody
transcription factor FOXP3
tumor necrosis factor alpha
unclassified drug
adoptive transfer
animal experiment
animal model
animal tissue
arthritis
article
CD4+ CD39+ FoxP3+ T lymphocyte
controlled study
cytokine production
disease severity
down regulation
female
gingiva
gingiva derived mesenchymal stem cell
histopathology
human
human cell
in vitro study
lymph node
lymphocyte differentiation
lymphocyte proliferation
mesenchymal stem cell
mouse
nonhuman
priority journal
regulatory T lymphocyte
signal transduction
spleen
synovial fluid
T cell depletion
T lymphocyte
Th1 cell
Th17 cell
Dentistry
Periodontics and Periodontology
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Abstract
Objective Current approaches offer no cures for rheumatoid arthritis (RA). Accumulating evidence has revealed that manipulation of bone marrow-derived mesenchymal stem cells (BM-MSCs) may have the potential to control or even prevent RA, but BM-MSC-based therapy faces many challenges, such as limited cell availability and reduced clinical feasibility. This study in mice with established collagen-induced arthritis (CIA) was undertaken to determine whether substitution of human gingiva-derived mesenchymal stem cells (G-MSCs) would significantly improve the therapeutic effects. Methods CIA was induced in DBA/1J mice by immunization with type II collagen and Freund's complete adjuvant. G-MSCs were injected intravenously into the mice on day 14 after immunization. In some experiments, intraperitoneal injection of PC61 (anti-CD25 antibody) was used to deplete Treg cells in arthritic mice. Results Infusion of G-MSCs in DBA/1J mice with CIA significantly reduced the severity of arthritis, decreased the histopathology scores, and down-regulated the production of inflammatory cytokines (interferon-γ and interleukin-17A). Infusion of G-MSCs also resulted in increased levels of CD4+CD39+FoxP3+ cells in arthritic mice. These increases were noted early after infusion in the spleens and lymph nodes, and later after infusion in the synovial fluid. The FoxP3+ Treg cells that were increased in frequency mainly consisted of Helios-negative cells. When Treg cells were depleted, infusion of G-MSCs partially interfered with the progression of CIA. Pretreatment of G-MSCs with a CD39 or CD73 inhibitor significantly reversed the protective effect of G-MSCs on CIA. Conclusion The role of G-MSCs in controlling the development and severity of CIA mostly depends on CD39/CD73 signals and partially depends on the induction of CD4+CD39+FoxP3+ Treg cells. G-MSCs provide a promising approach for the treatment of autoimmune diseases. Copyright © 2013 by the American College of Rheumatology.