Title: Hematopoietic Stem Cell Transplantation for the Treatment of Autoimmunity in Type 1 Diabetes
Volume: 6
Issue: 1
Author(s): Samuel A. LoCascio, Joia Spinelli and Josef Kurtz
Affiliation:
Keywords:
Diabetes, tolerance, chimerism, allogeneic, hematopoietic, pancre-atic cells., hematopoietic stem cell transplantation, pancreatic islet transplantation, autoimmune diseases (ADs), self-antigens,, sclerosis, systemic lupus erythematosus., insulin, major histocompatibility complex (MHC), rheumatoid arthritis, CTLA-4 gene, apoptosis, diabetogenic T cell, cytokines, bystander activation,, Lyme, Epstein-Barr, mumps, rubella, hygiene hypothesis, thyroiditis, vitamin B12, pernicious anemia, hypoglycemia, lymphocyte, tu-morigenesis, leukemias, lymphomas, ameliorate, non-myeloablative regimens, lymphohematopoietic, graft-versus-host disease, thymocytes, type-1 T regulatory (Tr1), natural killer T (NKT), histocompatibility barriers, hematopoietcially-derived antigens, thymus, costimulatory blockade), autoimmunity, myeloablation, experimental allergic en-cephalomyelitis, cyclophosphamide,, busulfan, thymectomy,, juvenile idiopathic arthritis, pancreatitis, glomerulonephritis, graft-versus-leukemia, insulitis, dendritic cells, macrophages, diabetogenesis, normoglycemia, immunosuppression, embryonic stem cells (ESCs)
Abstract: Type 1 diabetes (T1D) is an autoimmune disease that leads to the destruction of the insulin-producing pancreatic β cells. While there is no current cure, recent work in the field of allogeneic hematopoietic stem cell transplantation (HSCT) and the induction of mixed chimerism, a state in which multilineage hematopoietic populations of both recipient and donor co-exist, has demonstrated that it is possible to provide protection from disease onset, as well as reverse the autoimmune state in spontaneously diabetic mice. Furthermore, the establishment of mixed chimerism induces donorspecific tolerance, providing the potential to normalize glucose regulation via pancreatic islet transplantation without the requirement of life-long immunosuppression. Current studies are aimed at understanding the mechanisms involved in both the reversal of autoimmunity and the induction of tolerance, with the aim of moving this promising approach to curing T1D into the clinic.
