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Betacellulin overexpression in mesenchymal stem cells induces insulin secretion in vitro and ameliorates streptozotocin-induced hyperglycemia in rats

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Betacellulin overexpression in mesenchymal stem cells induces insulin secretion in vitro and ameliorates streptozotocin-induced hyperglycemia in rats

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Título Betacellulin overexpression in mesenchymal stem cells induces insulin secretion in vitro and ameliorates streptozotocin-induced hyperglycemia in rats
Autor Paz, Ana Helena da Rosa
Salton, Gabrielle Dias
Lugo, Ana Ilda Ayala
Gomes, Cristiano
Terraciano, Paula Barros
Scalco, Rosana
Laurino, Claudia Cilene Fernandes Correia
Passos, Eduardo Pandolfi
Schneider, Marlon Roberto
Meurer, Luíse
Cirne Lima, Elizabeth Obino
Abstract Betacellulin (BTC), a ligand of the epidermal growth factor receptor, has been shown to promote growth and differentiation of pancreatic b-cells and to improve glucose metabolism in experimental diabetic rodent models. Mesenchymal stem cells (MSCs) have been already proved to be multipotent. Recent work has attributed to rat and human MSCs the potential to differentiate into insulin-secreting cells. Our goal was to transfect rat MSCs with a plasmid containing BTC cDNA to guide MSC differentiation into insulin-producing cells. Prior to induction of cell MSC transfection, MSCs were characterized by flow cytometry and the ability to in vitro differentiate into mesoderm cell types was evaluated. After rat MSC characterization, these cells were electroporated with a plasmid containing BTC cDNA. Transfected cells were cultivated in Dulbecco’s modified Eagle medium high glucose (H-DMEM) with 10mMnicotinamide. Then, the capability ofMSC-BTC to produce insulin in vitro and in vivo was evaluated. It was possible to demonstrate by radioimmunoassay analysis that 104 MSC-BTC cells produced up to 0.4 ng=mL of insulin, whereas MSCs transfected with the empty vector (negative control) produced no detectable insulin levels. Moreover, MSC-BTC were positive for insulin in immunohistochemistry assay. In parallel, the expression of pancreatic marker genes was demonstrated by molecular analysis of MSC-BTC. Further, when MSCBTC were transplanted to streptozotocin diabetic rats, BTC-transfected cells ameliorated hyperglycemia from over 500 to about 200mg=dL at 35 days post-cell transplantation. In this way, our results clearly demonstrate that BTC overabundance enhances glucose-induced insulin secretion in MSCs in vitro as well as in vivo.
Contido em Stem cells and development. Larchmont (NY). Vol. 20, no. 2 (Feb. 2011), p. 223-232
Assunto Diabetes mellitus experimental
Diferenciação celular
Estreptozocina
Hiperglicemia
Insulina
Transplante de células-tronco mesenquimais
Origem Estrangeiro
Tipo Artigo de periódico
URI http://hdl.handle.net/10183/83598
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