Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version

5-2013

Publication Source

Arthritis and Rheumatism

Volume

65

Issue

5

Start Page

1181

Last Page

1193

DOI

10.1002/art.37894

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.

Comments

At the time of publication, author Qunzhou Zhang was affiliated with Division of Rheumatology and Immunology, University of Southern California. 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 Division of Rheumatology and Immunology, University of Southern California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.

Keywords

5'-Nucleotidase, 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

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Date Posted: 10 February 2023