[Treatment of type 1 diabetes by transplantation of bone-derived mesenchymal stem cells expressing human insulin gene: experiment with mice].
OBJECTIVE
To evaluate the effect of treatment of type 1 diabetes by transplantation of bone-derived stem cells expressing human insulin gene.


METHODS
Murine bone marrow-derived stem cells expressing green fluorescent protein (GFP-mMSCs) were isolated from 4/6-week-old GFP mice and transfected with a recombinant retrovirus-murine stem cell virus (MSCV) encoding human insulin gene, thus constructing the GFP-mMSCs-MCV-insulin. 16 C57BL/6J mice were injected with streptozotocin so as to establish models of type 1 diabetes and then randomly divided into 4 equal groups: Group A, undergoing injection into the liver with GFP-mMSC-MCV-insulin 1 week after the establishment of the model, Group B, undergoing intrahepatic transplantation of the GFP-mMSCs transfected with blank vector, Group C, undergoing intrahepatic transplantation of untransfected GFP-mMSCs, and Group D, undergoing intrahepatic transplantation of phosphate-buffered saline (PBS). Another 4 normal mice were used as controls and underwent intrahepatic transplantation of PBS too. After the transplantation the blood glucose, serum insulin, and body weight were detected everyday. 6 weeks later immunohistochemistry was used to detect the expression of human insulin in the mice liver tissues.


RESULTS
The body weight of Group A increased by 6% within 6 weeks after treatment, and the average blood glucose level 7 d and 42 d after transplantation were (10.4 +/- 2.8) mmol/L and (6.5 +/- 0.9) mmol/L respectively, both significantly lower than those of Group D [(26.8 +/- 2.5) mmol/L and (25.4 +/- 4.1) mmol/L respectively, both P < 0.05]. Immunohistochemistry showed secretion of human insulin in serum and liver.


CONCLUSIONS
The clinical manifestations of diabetes can be relieved effectively by intrahepatic transplantation of mMSCs expressing human insulin gene. This study implies a novel approach of gene therapy for type 1 diabetes.
Xu
Jian
J
Department of General Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
Zhu
Ming-Yan
MY
Lu
Yu-Hua
YH
Lu
Yang
Y
Wang
Zhi-Wei
ZW
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000601:surgery* / Q000628:therapy; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011897:Random Allocation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001786:Blood Glucose; D007328:Insulin; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins