Reversal of hyperglycemia in diabetic rats by portal vein transplantation of islet-like cells generated from bone marrow mesenchymal stem cells.
OBJECTIVE
To study the capacity of bone marrow mesenchymal stem cells (BM-MSCs) trans-differentiating into islet-like cells and to observe the effect of portal vein transplantation of islet-like cells in the treatment of streptozotocin-induced diabetic rat.


METHODS
BM-MSCs were isolated from SD rats and induced to differentiate into islet-like cells under defined conditions. Differentiation was evaluated with electron microscopy, RT-PCR, immunofluorescence and flow cytometry. Insulin release after glucose challenge was tested with ELISA. Then allogeneic islet-like cells were transplanted into diabetic rats via portal vein. Blood glucose levels were monitored and islet hormones were detected in the liver and pancreas of the recipient by immunohistochemistry.


RESULTS
BM-MSCs were spheroid adherent monolayers with high CD90, CD29 and very low CD45 expression. Typical islet-like cells clusters were formed after induction. Electron microscopy revealed that secretory granules were densely packed within the cytoplasm of the differentiated cells. The spheroid cells expressed islet related genes and hormones. The insulin-positive cells accounted for 19.8% and mean fluorescence intensity increased by 2.6 fold after induction. The cells secreted a small amount of insulin that was increased 1.5 fold after glucose challenge. After transplantation, islet-like cells could locate in the liver expressing islet hormones and lower the glucose levels of diabetic rats during d 6 to d 20.


CONCLUSIONS
Rat BM-MSCs could be transdifferentiated into islet-like cells in vitro. Portal vein transplantation of islet-like cells could alleviate the hyperglycemia of diabetic rats.
Wu
Xiao-Hong
XH
Department of Endocrinology, First affiliated hospital of Nanjing Medical University, 300 Guang-zhou Road, Nanjing 210029, Jiangsu Province, China.
Liu
Cui-Ping
CP
Xu
Kuan-Feng
KF
Mao
Xiao-Dong
XD
Zhu
Jian
J
Jiang
Jing-Jing
JJ
Cui
Dai
D
Zhang
Mei
M
Xu
Yu
Y
Liu
Chao
C
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D005260:Female; D006943:Hyperglycemia / Q000628:therapy*; D016381:Islets of Langerhans Transplantation; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D013311:Streptozocin