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.

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 beta-cell specific promoter. We treated some of the recipients with an agent toxic to beta-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 beta-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 beta-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 beta-cell lesion and mobilization induced by cytokines. Interestingly, however, treatment by cytokines may have beneficial indirect effects on STZ-induced hyperglycaemia.