Bibliographic Details
| Title: |
Betacellulin Overexpression in Mesenchymal Stem Cells Induces Insulin Secretion In Vitro and Ameliorates Streptozotocin-Induced Hyperglycemia in Rats. |
| Authors: |
Ana H. Paz, Gabrielle Dias Salton, Ana Ayala-Lugo, Cristiano Gomes, Paula Terraciano, Rosana Scalco, Claudia Cilene Fernandes Correia Laurino, Eduardo Pandolfi Passos, Marlon R. Schneider, Luise Meurer, Elizabeth Cirne-Lima |
| Source: |
Stem Cells & Development. Feb2011, Vol. 20 Issue 2, p223-232. 10p. |
| Subject Terms: |
*MESENCHYMAL stem cells, *INSULIN, *STREPTOZOTOCIN, *HYPERGLYCEMIA, *LABORATORY rats, *LIGANDS (Biochemistry), *EPIDERMAL growth factor, *NICOTINAMIDE |
| Abstract: |
Betacellulin (BTC), a ligand of the epidermal growth factor receptor, has been shown to promote growth and differentiation of pancreatic β-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 BTCcDNA 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 BTCcDNA. Transfected cells were cultivated in Dulbecco's modified Eagle medium high glucose (H-DMEM) with 10 mM nicotinamide. Then, the capability of MSC-BTCto produce insulin in vitro and in vivo was evaluated. It was possible to demonstrate by radioimmunoassay analysis that 104MSC-BTCcells 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-BTCwere positive for insulin in immunohistochemistry assay. In parallel, the expression of pancreatic marker genes was demonstrated by molecular analysis of MSC-BTC. Further, when MSC-BTCwere transplanted to streptozotocin diabetic rats, BTC-transfected cells ameliorated hyperglycemia from over 500 to about 200 mg/dL at 35 days post-cell transplantation. In this way, our results clearly demonstrate that BTCoverabundance enhances glucose-induced insulin secretion in MSCs in vitro as well as in vivo. [ABSTRACT FROM AUTHOR] |
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