Basic Research
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 28, 2007; 13(24): 3342-3349
Published online Jun 28, 2007. doi: 10.3748/wjg.v13.i24.3342
Reversal of hyperglycemia in diabetic rats by portal vein transplantation of islet-like cells generated from bone marrow mesenchymal stem cells
Xiao-Hong Wu, Cui-Ping Liu, Kuan-Feng Xu, Xiao-Dong Mao, Jian Zhu, Jing-Jing Jiang, Dai Cui, Mei Zhang, Yu Xu, Chao Liu
Xiao-Hong Wu, Cui-Ping Liu, Kuan-Feng Xu, Xiao-Dong Mao, Jian Zhu, Jing-Jing Jiang, Dai Cui, Mei Zhang, Yu Xu, Chao Liu, Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Author contributions: All authors contributed equally to the work.
Supported by Medical Key Subject grants (2001-34) from Jiangsu Province of China
Correspondence to: Chao Liu, Department of Endocrinology First affiliated hospital of Nanjing Medical University 300 Guang-zhou Road, Nanjing 210029, Jiangsu Province, China. drliuch@medmail.com
Telephone: +86-25-83718836-6530 Fax: +86-25-83674006
Received: January 19, 2007
Revised: February 3, 2007
Accepted: February 8, 2007
Published online: June 28, 2007
Abstract

AIM: To study the capacity of bone marrow mesenchymal stem cells (BM-MSCs) trans-differentiating into islet-like cells and to observe the effect of portal vein transplantation of islet-like cells in the treatment of streptozotocin-induced diabetic rat.

METHODS: BM-MSCs were isolated from SD rats and induced to differentiate into islet-like cells under defined conditions. Differentiation was evaluated with electron microscopy, RT-PCR, immunofluorescence and flow cytometry. Insulin release after glucose challenge was tested with ELISA. Then allogeneic islet-like cells were transplanted into diabetic rats via portal vein. Blood glucose levels were monitored and islet hormones were detected in the liver and pancreas of the recipient by immunohistochemistry.

RESULTS: BM-MSCs were spheroid adherent monolayers with high CD90, CD29 and very low CD45 expression. Typical islet-like cells clusters were formed after induction. Electron microscopy revealed that secretory granules were densely packed within the cytoplasm of the differentiated cells. The spheroid cells expressed islet related genes and hormones. The insulin-positive cells accounted for 19.8% and mean fluorescence intensity increased by 2.6 fold after induction. The cells secreted a small amount of insulin that was increased 1.5 fold after glucose challenge. After transplantation, islet-like cells could locate in the liver expressing islet hormones and lower the glucose levels of diabetic rats during d 6 to d 20.

CONCLUSION: Rat BM-MSCs could be transdiffe-rentiated into islet-like cells in vitro. Portal vein transplantation of islet-like cells could alleviate the hyperglycemia of diabetic rats.

Keywords: Bone marrow mesenchymal stem cells; Trans-differentiation; Islet; Insulin; Transplantation