Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen‐induced arthritis
TLDR
The results suggest an effective new therapeutic approach to target the pathogenic mechanism of autoimmune arthritis using allogeneic MSCs, which exerted their immunomodulatory function by educating antigen-specific Tregs.Abstract:
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 α was significantly decreased. MSCs exerted their immunomodulatory function by educating antigen-specific Tregs.
Conclusion
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.read more
Citations
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References
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Pluripotency of mesenchymal stem cells derived from adult marrow
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TL;DR: Based on the pathogenic mechanisms, specific therapeutic interventions can be designed to suppress synovial inflammation and joint destruction in rheumatoid arthritis.
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Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli
Massimo Di Nicola,Carmelo Carlo-Stella,Michele Magni,Marco Milanesi,Paolo Longoni,Paola Matteucci,Salvatore Grisanti,Alessandro M. Gianni +7 more
TL;DR: The data demonstrate that autologous or allogeneic BMSCs strongly suppress T-lymphocyte proliferation, this phenomenon that is triggered by both cellular as well as nonspecific mitogenic stimuli has no immunologic restriction, and T-cell inhibition is not due to induction of apoptosis and is likely due to the production of soluble factors.
Journal ArticleDOI
Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells
Katarina Le Blanc,Ida Rasmusson,Berit Sundberg,Cecilia Götherström,Moustapha Hassan,Mehmet Uzunel,Olle Ringdén +6 more
TL;DR: It is postulate that mesenchymal stem cells have a potent immunosuppressive effect in vivo and are transplanted in a patient with severe treatment-resistant grade IV acute graft-versus-host disease of the gut and liver.
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Adult rat and human bone marrow stromal cells differentiate into neurons
TL;DR: Adult marrow stromal cells can be induced to overcome their mesenchymal commitment and may constitute an abundant and accessible cellular reservoir for the treatment of a variety of neurologic diseases.