Induction of Central Tolerance

The induction of hematopoietic mixed chimerism, defined as the coexistence of donor and recipient hematopoietic cells, could be an approach to induce robust central tolerance. This strategy capitalizes on the use of nonmyeloablative hematopoietic stem cell transplantation (HSCT) prior to injection of myogenic stem cells from the donor HST (Parker et al. 2008). In this study two irradiated GRMD dogs with established full or partial chimerism first achieved at 11-26 months, were injected with donor-specific muscle-derived cells. The recipient dogs were transiently immunosuppressed with cyclosporine for 40 days. Local dystro-phin expression, up to 6.5% of normal levels, was sustained for periods up to 24 months post injection. This strategy is promising, as novel developments in the area of nonmyeloablative HSCT are ongoing for other cell-based therapies for benign diseases. Induction of central tolerance by intrathymic injection of viral vectors has been tested in rodents, and offers alternatives to antigen-specific tolerance (Ilan et al. 1996; Marodon et al. 2006).

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