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Vol. 26 No. 11 (2014): Vol 26 Issue 11

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Generation of Insulin-Producing Cells from Bone Marrow Mesenchymal Stem Cells with Modified Expression of PDX1 and NKX6.1

https://doi.org/10.14233/ajchem.2014.17541
Xiao-Long Tang
Stem Cell Engineering Research Center, School of Medical, Anhui University of Science & Technology, Huainan 232001, P.R. China ;Nankai Hospital, Nankai Clinical School, Tianjin Medical University, Tianjin 300100, P.R. China
Ze-Ming Wan
Clinical Laboratory, Second Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine (Guangdong Provincial Hospital of TCM), Guangzhou 510120, P.R. China
Yun-Long Gao
Clinical Laboratory, Second Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine (Guangdong Provincial Hospital of TCM), Guangzhou 510120, P.R. China
Cheng Zhang
Clinical Laboratory, Second Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine (Guangdong Provincial Hospital of TCM), Guangzhou 510120, P.R. China
Xian-Zhang Huang
Clinical Laboratory, Second Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine (Guangdong Provincial Hospital of TCM), Guangzhou 510120, P.R. China
Li-Fa Xu
1Stem Cell Engineering Research Center, School of Medical, Anhui University of Science & Technology, Huainan 232001, P.R. China
Zhen Huo
1Stem Cell Engineering Research Center, School of Medical, Anhui University of Science & Technology, Huainan 232001, P.R. China
Tian-Yi Chen
1Stem Cell Engineering Research Center, School of Medical, Anhui University of Science & Technology, Huainan 232001, P.R. China
Shu-Yu Cai
Stem Cell Engineering Research Center, School of Medical, Anhui University of Science & Technology, Huainan 232001, P.R. China; Nankai Hospital, Nankai Clinical School, Tianjin Medical University, Tianjin 300100, P.R. China
Zhen-You Jiang
Department of Microbiology and Immunology, School of Medical, Jinan University, Guangzhou 510632, P.R. China
Jia Chen
Department of Microbiology and Immunology, School of Medical, Jinan University, Guangzhou 510632, P.R. China
Liu-Hua Wei
Clinical Laboratory, Liuzhou worker’s Hospital, Guangxi 545005, P.R. China
Jian Wang
Stem Cell Engineering Research Center, School of Medical, Anhui University of Science & Technology, Huainan 232001, P.R. China
Xiao-Yin Chen
Department of Microbiology and Immunology, School of Medical, Jinan University, Guangzhou 510632, P.R. China

Corresponding Author(s) : Jian Wang

txljd2006@126.com

Asian Journal of Chemistry, Vol. 26 No. 11 (2014): Vol 26 Issue 11

Abstract

This study was designed to efficiently induce the differentiation of the bone marrow mesenchymal stem cells (BMSCs) into insulin-producing islet cells by modifying the expression of pancreatic and duodenal homeobox factor 1 (PDX1) and NKX6 transcription factor related 1 (NKX6.1). Bone marrow mesenchymal stem cells were infected by the recombinant adeno viruses carrying Pdx1 and Nkx6.1 genes for differentiation and the differentiated cells were transplanted into the subrenal capsule of diabetic mice, then the secretion of insulin and C-peptide were examined. The effects of the differentiated cells were also investigated through measuring the blood glucose levels. The BMSCs induced by recombinant adeno virus of pAdxsi-CMV-PDX1/CMV-NKX6.1 and several cytokines showed positive dithizone staining and significant expression of insulin and glucose transporter-2. Stimulation with different levels of glucose caused different insulin secretion levels at 1240.4 ± 109.3 and 3539.8 ± 245.1 mU/L with 5.5 and 25 mmol/L treatments, respectively. More importantly, the transplantation of induced cells recovered the serum glucose in Streptozotocin mice to normal levels. Coexpression of exogenous PDX-1 and NKX6.1 efficiently induced the differentiation of BMSCs into insulin-producing cells, which restored the blood glucose levels in STZ-induced diabetic mice.

Keywords

Pancreatic and duodenal homeobox factor 1 Adeno virus vector Insulin-producing cells Gene-modification
Tang, X.-L., Wan, Z.-M., Gao, Y.-L., Zhang, C., Huang, X.-Z., Xu, L.-F., … Chen, X.-Y. (2014). Generation of Insulin-Producing Cells from Bone Marrow Mesenchymal Stem Cells with Modified Expression of PDX1 and NKX6.1. Asian Journal of Chemistry, 26(11), 3417–3424. https://doi.org/10.14233/ajchem.2014.17541
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