Expression of Pdx -1 in bone marrow mesenchymal stem cells promotes differentiation of islet-like cells in vitro |
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Authors: | SUN Jiping YANG Yujia WANG Xiaoli SONG Jianhui JIA Yanjie |
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Institution: | 1. Department of Pediatrics, Xiang-Ya Hospital, Central-South University, Changsha 410008, China 2. Department of Neurology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China |
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Abstract: | Bone marrow mesenchymal stem cells (BMSCs) have the ability of self-renewal and multi-directional differentiation. Recent
reports showed that BMSCs could differentiate into endocrine cells of pancreas. However, the differentiation is not efficient
enough to produce insulin-producing cells for the future therapeutic use. Pdx-1 is a crucial regulator for pancreatic development. Therefore we constructed a eukaryotic expression vector containing Pdx-1 to determine the effect of Pdx-1 expression on differentiation of BMSCs in vitro. The results showed that BMSCs could self-assemble to form functional pancreatic islet-like structures after differentiation
in vitro. The proportion of insulin-producing cells differentiated from Pdx-1+BMSCs was 28.23%±2.56%, higher than that from BMSCs transfected with vacant vector and Pdx-1 − BMSCs (7.23%±1.56% and 4.08%±2.69% respectively) by flow cytometry. Immunocytochemical examination also testified the expression
of multiple β-cells-specific genes such as insulin, glucagons, somatostatin in differentiated BMSCs. The results also revealed
that the expressions of genes mentioned above in Pdx-1+BMSCs were higher than that in Pdx-1−BMSCs, which was confirmed by Western blotting analysis and RT-PCR. Glucose-induced insulin secretion from Pdx-1+BMSCs in 5mmol/L and 25mmol/L glocuse was (56.61±4.82) μU/mL and (115.29±2.56) μU/mL respectively, which were much higher
than those from Pdx-1−BMSCs((25.53±6.49) μU/mL and (53.26±7.56) μU/mL respectively). Grafted animals were able to maintain their body weight and
survive for relatively longer periods of time than hyperglycemic sham-grafted controls, which demonstrated an overall beneficial
effect of the grafted cells on the health of the animals. These findings thus suggested that exogenous expression of Pdx-1 should provide a promising approach for efficiently producing islet-like cells from BMSCs for the future therapeutic use
in diabetic patients. |
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Keywords: | bone marrow mesenchymal stem cells islet of Langerhans pancreatic duodenal homeobox 1 diabetes |
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