Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis.
OBJECTIVE
Mesenchymal stem cells (MSCs) are precursors of tissue of mesenchymal origin, but they also have the capacity to regulate the immune response by suppressing T and B lymphocyte proliferation in a non-major histocompatibility complex-restricted manner. Use of MSCs as immunosuppressant agents in autoimmune diseases has been proposed and successfully tested in animal models. We explored the feasibility of using allogeneic MSCs as therapy for collagen-induced arthritis, a mouse model for human rheumatoid arthritis.


METHODS
DBA/1 mice were immunized with type II collagen in Freund's complete adjuvant, and some of the animals received an intraperitoneal injection of allogeneic MSCs.


RESULTS
A single injection of MSCs prevented the occurrence of severe, irreversible damage to bone and cartilage. MSCs induced hyporesponsiveness of T lymphocytes as evidenced by a reduction in active proliferation, and modulated the expression of inflammatory cytokines. In particular, the serum concentration of tumor necrosis factor alpha was significantly decreased. MSCs exerted their immunomodulatory function by educating antigen-specific Tregs.


CONCLUSIONS
Our results suggest an effective new therapeutic approach to target the pathogenic mechanism of autoimmune arthritis using allogeneic MSCs. However, further studies are required before these results can be translated to clinical settings.
Augello
Andrea
A
Department of Oncology, Biology, and Genetics, University of Genoa, National Institute for Cancer Research, Genoa, Italy.
Tasso
Roberta
R
Negrini
Simone Maria
SM
Cancedda
Ranieri
R
Pennesi
Giuseppina
G
D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D001854:Bone Marrow Cells; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D005260:Female; D007596:Joints / Q000187:drug effects* / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous
D016207:Cytokines