Jian Xu1, Yuhua Lu1, Fei Ding2, Xi Zhan3, Mingyan Zhu1, Zhiwei Wang4. 1. Department of General Surgery, the Affiliated Hospital, Nantong University, Nantong, Jiangsu Province, China, 226001. 2. Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China, 226001. 3. Greenebaum Cancer Center, School of Medicine, University of Maryland, Baltimore, USA. 4. Department of General Surgery, the Affiliated Hospital, Nantong University, Nantong, Jiangsu Province, China, 226001. dxjqhy@yahoo.com.cn.
Abstract
BACKGROUND: The objective of this study was to assess the effect of intrahepatic injection of bone-derived green fluorescent protein (GFP)-transgenic murine mesenchymal stem cells (GFP-mMSCs) containing the human insulin(ins) gene in streptozotocin-induced diabetic mice. METHODS: GFP-mMSCs were isolated from the bone marrow of GFP transgenic mice, expanded, and transfected with a recombinant retrovirus MSCV carrying the human insulin gene. C57BL/6J mice were made diabetic by an intraperitoneal administration of 160 mg/kg streptozotocin (STZ), followed by intrahepatic injection of transfected GFP-mMSCs. The variations in body weight and the blood glucose and serum insulin levels were determined after cell transplantation. GFP-mMSCs survival and human insulin expression in liver tissues were examined by fluorescent microscopy and immunohistochemistry. RESULTS: The body weight in diabetic mice that received GFP-mMSCs harboring the human insulin gene was increased by 6% within 6 weeks after treatment, and the average blood glucose levels in these animals were 10.40 +/- 2.80 mmol/l (day 7) and 6.50 +/- 0.89 mmol/l (day 42), respectively, while the average values of blood glucose in diabetic animals without treatment were 26.80 +/- 2.49 mmol/l (day 7) and 25.40 +/- 4.10 mmol/l (day 42), showing a significant difference (p < 0.05). Moreover, secretion of human insulin of GFP-mMSCs in serum and animal liver was detected by radioimmunoassay (RIA) and immunohistochemistry (IHC). CONCLUSIONS: Experimental diabetes could be relieved effectively for up to 6 weeks by intrahepatic transplantation of murine mesenchymal stem cells expressing human insulin. This study implies a novel approach of gene therapy for type I diabetes.
BACKGROUND: The objective of this study was to assess the effect of intrahepatic injection of bone-derived green fluorescent protein (GFP)-transgenic murine mesenchymal stem cells (GFP-mMSCs) containing the humaninsulin(ins) gene in streptozotocin-induced diabeticmice. METHODS: GFP-mMSCs were isolated from the bone marrow of GFP transgenic mice, expanded, and transfected with a recombinant retrovirus MSCV carrying the humaninsulin gene. C57BL/6J mice were made diabetic by an intraperitoneal administration of 160 mg/kg streptozotocin (STZ), followed by intrahepatic injection of transfected GFP-mMSCs. The variations in body weight and the blood glucose and serum insulin levels were determined after cell transplantation. GFP-mMSCs survival and humaninsulin expression in liver tissues were examined by fluorescent microscopy and immunohistochemistry. RESULTS: The body weight in diabeticmice that received GFP-mMSCs harboring the humaninsulin gene was increased by 6% within 6 weeks after treatment, and the average blood glucose levels in these animals were 10.40 +/- 2.80 mmol/l (day 7) and 6.50 +/- 0.89 mmol/l (day 42), respectively, while the average values of blood glucose in diabetic animals without treatment were 26.80 +/- 2.49 mmol/l (day 7) and 25.40 +/- 4.10 mmol/l (day 42), showing a significant difference (p < 0.05). Moreover, secretion of humaninsulin of GFP-mMSCs in serum and animal liver was detected by radioimmunoassay (RIA) and immunohistochemistry (IHC). CONCLUSIONS: Experimental diabetes could be relieved effectively for up to 6 weeks by intrahepatic transplantation of murine mesenchymal stem cells expressing humaninsulin. This study implies a novel approach of gene therapy for type I diabetes.
Authors: I D Goldfine; M S German; H C Tseng; J Wang; J L Bolaffi; J W Chen; D C Olson; S S Rothman Journal: Nat Biotechnol Date: 1997-12 Impact factor: 54.908
Authors: A T Cheung; B Dayanandan; J T Lewis; G S Korbutt; R V Rajotte; M Bryer-Ash; M O Boylan; M M Wolfe; T J Kieffer Journal: Science Date: 2000-12-08 Impact factor: 47.728
Authors: Maria Giovanna Francipane; Melchiorre Cervello; Giovanni Battista Vizzini; Giada Pietrosi; Giuseppe Montalto Journal: Cell Med Date: 2011-06-01