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 | Jian Xu, Yuhua Lu, Fei Ding, Xi Zhan, Mingyan Zhu, Zhiwei Wang |
Journal | World journal of surgery
(World J Surg)
Vol. 31
Issue 9
Pg. 1872-1882
(Sep 2007)
ISSN: 0364-2313 [Print] United States |
PMID | 17653584
(Publication Type: Journal Article)
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Chemical References |
- Hypoglycemic Agents
- Insulin
- Green Fluorescent Proteins
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Topics |
- Animals
- Bone and Bones
- Diabetes Mellitus, Experimental
(chemically induced, therapy)
- Disease Models, Animal
- Genetic Therapy
(methods)
- Genetic Vectors
- Green Fluorescent Proteins
(genetics)
- Humans
- Hypoglycemic Agents
- Injections
(methods)
- Insulin
(genetics)
- Liver
(metabolism)
- Mesenchymal Stem Cell Transplantation
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Recombination, Genetic
- Retroviridae
(genetics)
- Treatment Outcome
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