Cytokine mobilization of bone marrow cells and pancreatic lesion do not improve streptozotocin-induced diabetes in mice by transdifferentiation of bone marrow cells into insulin-producing cells

Abstract

Objective Transdifferentiation of bone marrow cells (BMC) into insulin-producing cells might provide a new cellular therapy for type I diabetes, but its existence is controversial. Our aim was to determine if those cells could transdifferentiate, even at low frequency, into insulin-producing cells, in testing optimized experimental conditions. Methods We grafted mice with total BMC, genetically labeled either ubiquitarily, or with a marker conditionally expressed under the control of the insulin β-cell specific promoter. We treated some of the recipients with an agent toxic to β-cells (streptozotocin) and with cytokines stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF). Results The contribution of grafted cells could be detected neither for natural turnover ( n = 6), nor for β-cell regeneration after pancreatic lesion ( n = 7), 90 days post-transplantation. Cytokine mobilization of BMC in the blood stream, reported to favor their transdifferentiation into cardiac and neural cells, had never been tested before for β-cell generation. Here, we showed that injection of SCF and G-CSF did not lead to a detectable level of transdifferentiation ( n = 7). Conclusions We conclude that BMC cannot spontaneously transdifferentiate into insulin-producing cells in vivo, even after β-cell lesion and mobilization induced by cytokines. Interestingly, however, treatment by cytokines may have beneficial indirect effects on STZ-induced hyperglycaemia.