Mesenchymal stem cells treated with rat pancreatic extract secrete cytokines that improve the glycometabolism of diabetic rats.
BACKGROUND
Mesenchymal stem cells (MSCs) under favorable conditions secrete a spectrum of cytokines that promote the survival of surrounding cells via paracrine mechanisms. We explored the impact of rat pancreatic extract (RPE) on cytokine secretion by MSCs and examined the influence of administration of conditioned media of MSCs treated with RPE on blood glucose levels in diabetic rats.


METHODS
Cytokine levels (IGF-1, VEGF, bFGF) in conditioned media of MSCs treated with RPE were measured using enzyme-linked immunosorbent assays. We estimated blood glucose levels of STZ-induced diabetic rats following intraperitoneal injection of conditioned media from RPE-treated MSCs. We analyzed histopathology of pancreatic islets by insulin immunostaining and apoptosis through a TUNEL assay.


RESULTS
Levels of IGF-1, VEGF, and bFGF were significantly increased in RPE-CM compared with control media. Administration of conditioned media of RPE-treated MSCs significantly lowered the blood glucose levels of diabetic rats. After RPE treatment the insulin-positive area was increased and apoptosis of pancreatic beta cells decreased.


CONCLUSIONS
RPE enhanced the secretion of cytokines by MSCs. MSCs in the pancreatic microenvironment may exert indirect salutary effects via paracrine mediators on injured pancreatic cells in an STZ-induced diabetic animal model. The secreted factors may exert their therapeutic benefits by preventing apoptosis of pancreatic beta cells.
Xu
Y-X
YX
Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, People's Republic of China.
Chen
L
L
Hou
W-K
WK
Lin
P
P
Sun
L
L
Sun
Y
Y
Dong
Q-Y
QY
Liu
J-B
JB
Fu
Y-L
YL
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D018929:Cell Culture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism* / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010179:Pancreas / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014020:Tissue Extracts / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000627:therapeutic use
D017077:Culture Media, Conditioned; D016207:Cytokines; D014020:Tissue Extracts; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I