Effects of intrahepatic bone-derived mesenchymal stem cells autotransplantation on the diabetic Beagle dogs.
BACKGROUND
To assess the effects of intrahepatic autotransplantation of bone-derived Beagle canine mesenchymal stem cells (BcMSCs) containing human insulin and EGFP in diabetic Beagle dogs.


METHODS
BcMSCs were isolated from Beagle canine bone marrow, expanded, and transfected with a recombinant retrovirus MSCV carrying human insulin and EGFP. Animals were made diabetic by an intravenous administration of streptozotocin (STZ, 30 mg/kg) and alloxan (50 mg/kg), followed by intrahepatic autotransplantation of transfected BcMSCs. The variations of body weight, blood glucose, serum insulin levels, and plasma C-peptide were determined after autotransplantation. BcMSCs' survival and human insulin expression in liver and serum were examined by fluorescent microscopy, radioimmunoassay (RIA), and immunohistochemistry (IHC).


RESULTS
The body weight of diabetic Beagle dogs received BcMSCs transplantation increased by 11.09% within 16 wk after treatment, and the average blood glucose levels were 19.80±3.13 mmol/L (d 7) and 9.78±3.11 mmol/L (d 112), while in untreated animals, the average values were 21.20±3.26 mmol/L (d 7) and 22.5±3.22 mmol/L (d 112), showing a significant difference (P<0.05). The detection of C-peptide excluded the possible function of regenerative β cells. However, glucose tolerance test revealed BcMSCs group response was not as efficient as that of normal islets, although they could respond to the glucose challenge.


CONCLUSIONS
Experimental diabetes could be relieved effectively for up to 16 wk by intrahepatic autotransplantation of BcMSCs expressing human insulin, which implies a novel approach of gene therapy for type I diabetes.
Zhu
Shajun
S
Department of General Surgery, The Affiliated Hospital, Nantong University, Nantong, Jiangsu Province, People's Republic of China.
Lu
Yuhua
Y
Zhu
Jianwei
J
Xu
Jian
J
Huang
Hua
H
Zhu
Mingyan
M
Chen
Yuquan
Y
Zhou
Yuan
Y
Fan
Xiangjun
X
Wang
Zhiwei
Z
D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D002096:C-Peptide / Q000378:metabolism; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D004285:Dogs; D005455:Fluorescent Antibody Technique; D015316:Genetic Therapy; D005822:Genetic Vectors; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D008099:Liver / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012190:Retroviridae; D014182:Transplantation, Autologous
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D011994:Recombinant Proteins