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Reversal of Diabetes in Mice by Intrahepatic Injection of Bone-derived GFP-murine Mesenchymal Stem Cells Infected with the Recombinant Retrovirus-carrying Human Insulin Gene

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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.

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Authors and Affiliations

  1. Department of General Surgery, the Affiliated Hospital, Nantong University, Nantong, Jiangsu Province, China, 226001

    Jian Xu, Yuhua Lu, Mingyan Zhu & Zhiwei Wang

  2. Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China, 226001

    Fei Ding

  3. Greenebaum Cancer Center, School of Medicine, University of Maryland, Baltimore, USA

    ** Zhan

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  1. Jian Xu
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  2. Yuhua Lu
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  3. Fei Ding
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  4. ** Zhan
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  5. Mingyan Zhu
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Correspondence to Zhiwei Wang.

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Xu, J., Lu, Y., Ding, F. et al. Reversal of Diabetes in Mice by Intrahepatic Injection of Bone-derived GFP-murine Mesenchymal Stem Cells Infected with the Recombinant Retrovirus-carrying Human Insulin Gene. World J Surg 31, 1872–1882 (2007). https://doi.org/10.1007/s00268-007-9168-2

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