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BACKGROUND The role of bone marrow (BM)-derived cells in pancreatic beta-cell regeneration remains unresolved. We examined whether BM-derived cells are recruited to the site of moderate pancreatic injury and contribute to beta-cell regeneration. METHODS Low-dose streptozotocin (STZ) treatment was used to induce moderate pancreatic damage and(More)
We show for the first time that signaling through the TLR4/TRIF pathway plays a critical role in allogeneic bone marrow cell (BMC) rejection. This appears to be unique to BMCs as organ allografts are rejected mainly via MyD88 signaling. Using T- or T-/B-cell-deficient mice, we found that BMC allorejection occurred early before T-cell activation and was T-(More)
IMPORTANCE OF THE FIELD β-Cell regeneration and β-cell preservation are two promising therapeutic approaches for the management of patients with type 1 diabetes (T1D). Stem cell-based strategies to address the problems of shortage in β cells, autoimmune and alloimmune responses have become an area of intense study. AREAS COVERED IN THIS REVIEW This review(More)
BACKGROUND Currently, the donor-recipient matching process for vascularized composite tissue allotransplantation (VCTA) closely follows the standard practices for solid organ transplantation. Sensitization is considered a contraindication to VCTA. However, the role of sensitization in VCTA rejection is largely unstudied. METHODS Major(More)
BACKGROUND FoxP3/CD4/CD25 regulatory T cells (Treg) play an important role in maintaining peripheral tolerance and are potent suppressors of T-cell activation. In this study, we evaluated the role of Treg in peripheral tolerance to composite tissue allografts (CTA). METHODS Mixed allogeneic chimeric rats were prepared by preconditioning recipients with(More)
BACKGROUND Mixed chimerism induces donor-specific tolerance to composite tissue allotransplants (CTAs). In the present studies, we used a nonmyeloablative conditioning approach to establish chimerism and promote CTA acceptance. METHODS Wistar Furth (RT1A(u)) rats were conditioned with 600 to 300 cGy total body irradiation (TBI, day-1), and 100 x 10(6)(More)
For over 50 y the association between hematopoietic chimerism and tolerance has been recognized. This originated with the brilliant observation by Dr. Ray Owen that freemartin cattle twins that shared a common placental blood supply were red blood cell chimeras, which led to the discovery that hematopoietic chimerism resulted in actively acquired tolerance.(More)
CD8(+) TCR(-) graft facilitating cells (FCs) enhance engraftment of hematopoietic stem cells (HSCs) in allogeneic and syngeneic recipients. The mechanisms by which FCs promote HSC engraftment and tolerance induction have not been fully elucidated. Here, we provide data to support a critical role for dedicator of cytokinesis 2 (DOCK2) in multiple aspects of(More)
OBJECTIVE Autoimmune diabetes can be reversed with mixed chimerism. However, the myelotoxic agents currently required to establish chimerism have prevented the translation of this approach to the clinic. Here, we investigated whether multimodal costimulatory blockade would enhance chimerism and promote islet allograft tolerance in spontaneously diabetic(More)
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