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.
Lavazais
E
E
Cellular and Molecular Immuno-Endocrinology, Inra/ENVN/University, Atlanpole, La Chantrerie, BP 40706, 44307 Nantes cedex 03, France.
Pogu
S
S
Saï
P
P
Martignat
L
L
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D016207:Cytokines / Q000494:pharmacology*; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000473:pathology* / Q000503:physiopathology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology*; D019089:Stem Cell Factor / Q000494:pharmacology; D001616:beta-Galactosidase / Q000172:deficiency
D001786:Blood Glucose; D016207:Cytokines; D017931:DNA Primers; D007328:Insulin; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D001616:beta-Galactosidase