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TISSUE-SPECIFIC STEM CELLS

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

Veronika S. Urbán^a, Judit Kiss^a, János Kovács^b, Elen Gócza^c, Virág Vas^a, va Monostori^d, Ferenc Uher^a

^aStem Cell Biology, National Medical Center, Budapest, Hungary;
^bDepartment of Anatomy, Cell and Developmental Biology, Loránd Eötvös University, Budapest, Hungary;
^cDepartment of Animal Biology, Agricultural Biotechnology Center, Gödöll, Hungary;
^dLymphocyte Signal Transduction Laboratory, Institute of Genetics, Biological Research Center of Hungarian Academy of Sciences, Szeged, Hungary

Key Words. Bone marrow • Diabetes • Immunosuppression • Mesenchymal stem cells • Streptozotocin • Transplantation

Correspondence: Ferenc Uher, Ph.D., National Medical Center, Stem Cell Biology, Diószegi ut 64, Budapest H-1113, Hungary. Telephone: 36-1-372-4334; Fax: 36-1-372-4352; e-mail: uher{at}kkk.org.hu

Received April 11, 2007; accepted for publication October 2, 2007.
First published online in STEM CELLS EXPRESS   October 11, 2007.



Several recent studies have suggested that the adult bone marrow harbors cells that can influence β-cell regeneration in diabetic animals. Other reports, however, have contradicted these findings. To address this issue, we used an animal model of type 1 diabetes in which the disease was induced with streptozotocin in mice. Freshly prepared sex-mismatched bone marrow cells (BMCs) and syngeneic or allogeneic mesenchymal stem cells (MSCs) were concomitantly administrated into sublethally irradiated diabetic mice. Blood glucose and serum insulin concentrations rapidly returned to normal levels, accompanied by efficient tissue regeneration after a single injection of a mixture of 10⁶ BMCs per 10⁵ MSCs. 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 β-cells were found in the recovered animals, indicating a graft-initiated endogenous repair process. Moreover, MSC injection caused the disappearance of β-cell-specific T lymphocytes from diabetic pancreas. Therefore, we suggest that two aspects of this successful treatment regimen operate in parallel 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 β-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.

Disclosure of potential conflicts of interest is found at the end of this article.