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Expression of Pdx-1 in bone marrow mesenchymal stem cells promotes differentiation of islet-like cells in vitro

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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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Authors and Affiliations

  1. Department of Pediatrics, Xiang-Ya Hospital, Central-South University, Changsha, 410008, China

    Sun Jiping, Yang Yujia, Wang Xiaoli & Song Jianhui

  2. Department of Neurology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, China

    Jia Yanjie

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  1. Sun Jiping
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  2. Yang Yujia
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  3. Wang Xiaoli
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  4. Song Jianhui
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Correspondence to Jia Yanjie.

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Sun, J., Yang, Y., Wang, X. et al. Expression of Pdx-1 in bone marrow mesenchymal stem cells promotes differentiation of islet-like cells in vitro . SCI CHINA SER C 49, 480–489 (2006). https://doi.org/10.1007/s11427-006-2016-z

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  • DOI: https://doi.org/10.1007/s11427-006-2016-z

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