Mesenchymal Stem Cells Cooperate with Bone Marrow Cells in Therapy of Diabetes

Veronika S. Urbán ¹, Judit Kiss ¹, János Kovács ², Elen Gócza ³, Virág Vas ¹, va Monostori ⁴, Ferenc Uher ^1*

¹ Stem Cell Biology, National Medical Center, Budapest, Hungary
² Department of Anatomy, Cell and Developmental Biology, Loránd Eötvös University, Budapest, Hungary
³ Department of Animal Biology, Agricultural Biotechnology Center, Gödöll, Hungary
⁴ Lymphocyte Signal Transduction Laboratory, Institute of Genetics, Biological Research Center of Hungarian Academy of Sciences, Szeged, Hungary

^* To whom correspondence should be addressed. E-mail: uher{at}kkk.org.hu.

	Abstract

Several recent studies have suggested that the adult bone marrow harbours cells that can influence -cell regeneration in diabetic animals. Other reports, however, contradicted these findings. To address this issue, we used an animal model of type 1 diabetes in which the disease was induced with streptozotocin (STZ) in mice. Freshly prepared sex-mismatched bone marrow cells (BMC) and syngeneic or allogeneic mesenchymal stem cells (MSC) were concomitantly administrated into sublethally irradiated diabetic mice. Blood glucose and serum insulin concentrations rapidly returned to normal levels accompanied with efficient tissue regeneration after a single injection of a mixture of 10⁶ BMC/10⁵MSCs. Neither BMC nor MSC transplantation was effective alone. Successful treatment of diabetic animals was not due to the reconstitution of the damaged islet cells from the transplant since no donor-derived -cells were found in the recovered animals, indicating a graft initiated endogenous repair process. Moreover, MSC injection caused the disappearance of -cell-specific T lymphocytes from diabetic pancreas. Therefore, we suggest that two aspects of this successful treatment regimen operate parallelly and synergistically in our model. First, BMCs and MSCs induce the regeneration of recipient derived pancreatic insulin-secreting cells. Second, MSCs inhibit T-cell-mediated immune responses against newly formed -cells which, in turn, are able to survive in this altered immunological milieu. Thus, the application of this therapy in human patients suffering from diabetes and/or other tissue destructive autoimmune diseases may be feasible.

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