Bone Marrow Stem Cell Transplantation Restores Heme Oxygenase and Antioxidants Genes and Pancreatic Function in Type 1 Diabetes.

Abstract

Type 1 diabetes is caused by the autoimmune destruction of pancreatic beta(β)cells has been linked to a decrease in circulating stem cells and increased superoxide (O2)secondary to a decrease in heme oxygenase (HO) activity. Decrease HO-1 increases oxidative stress, resulting in β-cell destruction. O2 and β-cell destruction. Nonobese diabetic (NOD) mice (2 months old), which undergo pancreatic T-cell infiltration resulting in elevated were irradiated and reconstituted with bone marrow stem cells from BALB/c mice(<2 months old) using a perfusion technique, exhibited neither insulitis nor overt diabetes. The newly developed T-cells in BMT recipients were tolerant to both donor and host major histocompatability complex determinants. After six months, BMT-treated mice showed the same glucose tolerance as age-matched controls, HO activity was restored to the level of age-matched controls, and EC-SOD protein levels returned to normal. The increased HO activity after BMT was accompanied by a significant elevation of HO-1 protein and a significant decrease in O2-levels(μmol/mg protein 1.16±0.37 μmol/mg protein versus 2.81±0.37 in nontransplant mice). These results demonstrate that bone marrow-derived stem cell transplant restored the antioxidant genes HO-1 and EC-SOD as well as pancreatic function. In addition, we demonstrate that combining BMT and islet cell transplant can restore insulin production in severely diabetic animals. We have thus demonstrated in this animal model of type 1 diabetes that BMT is effective as both a preventive and therapeutic treatment.