Regression of adjuvant-induced arthritis in rats following bone marrow transplantation.

Abstract

Total body irradiation followed by bone marrow transplantation was found to be an effective treatment for adjuvant arthritis induced in rats. This treatment is most effective when applied shortly after the clinical manifestation of arthritis--i.e., 4-7 weeks after administration of Mycobacterium tuberculosis. Transplantation of bone marrow at a later stage results in a limited recovery, in that the inflammatory reaction regresses but the newly formed excessive bone is not eliminated. Local irradiation of the affected joints had no effect on the disease. It could also be excluded that the recovery of arthritis following marrow transplantation is due to lack of available antigen. Transplantation of syngeneic bone marrow is as effective as that of allogeneic bone marrow from a rat strain that is not susceptible to induction of adjuvant arthritis. The beneficial effect of this treatment cannot be ascribed to the immunosuppressive effect of total body irradiation, since treatment with the highly immunosuppressive drug Cyclosporin A resulted in a regression of the joint swelling but relapse occurred shortly after discontinuation of the treatment.

Tolerance induction with gene-modified stem cells and immune-preserving conditioning in primed mice: restricting antigen to differentiated antigen-presenting cells permits efficacy

“…Alternatively, myeloablative and nonmyeloablative conditioning are highly immune-depleting, and used in conjunction with autologous HSCT (aHSCT) for recovery of hematopoiesis, can provide an "immunologic reset." This avoids the risks of allogeneic BMT/HSCT and subsequent GVHD but alleviates autoimmune disease experimentally [2][3][4] and clinically (reviewed by Coleman and Steptoe 5 ). In multiple sclerosis, approximately 70% of patients treated with aHSCT remain progression-free 3 years after treatment.…”

Hematopoietic Cell Transplantation for Autoimmune Diseases: A Review of History, Current State, and Future Issues

“…It was clearly shown that the transplantation protects the cited conditions from relapse [10][11][12]. Similar effect was shown in autoimmune diseases with other target organs [13].…”

Induction of antigen-specific tolerance through hematopoietic stem cell-mediated gene therapy: The future for therapy of autoimmune disease?

“…Autologous HSCT, however, avoids GVHD and other risks associated with allogeneic or MHC-mismatched HSCT, making it more applicable to clinical use for autoimmune diseases. Syngeneic and autologous HSCT was tested in animal models and found effective in EAE and experimental arthritis [29][30][31].…”