Time Point Is Important for Effects of Syngeneic Bone Marrow Transplantation for Type 1 Diabetes in Mice

ObjectivesAutologous hematopoietic stem cell transplantation (HSCT) has recently become a novel therapy for patients with new-onset type 1 diabetes (T1D). However, the optimal time points for HSCT are still unknown.MethodsBy using multiple low-dose streptozotocin (STZ)-induced T1D mice models, we performed syngeneic bone marrow transplantation (syn-BMT) in diabetic mice at various time points new-onset day 3 (n = 12); new-onset day 10 (n = 13); later-onset day 20 (n = 12); and day 40 (n = 7), respectively. At 120 days after syn-BMT, we examined pancreata histology, serum insulin, and CD4+CD25+FoxP3+ T regulatory lymphocytes (Tregs).ResultsOur previous results showed that syn-BMT can overcome diabetes when performed on day 10, but not at day 40. Our new data showed BMT only attenuated diabetes when done on day 3 or day 20. Moreover, the percentage of Tregs in the spleen correlated with the attenuation of hyperglycemia.SignificanceThese results indicated that syn-BMT should be performed, when diabetes is neither too new-onset nor too late-stage. Tregs represent one mechanism for syn-BMT-induced restoration of immune tolerance in STZ-diabetic mice.