In-vitro promoted differentiation of mesenchymal stem cells towards hepatocytes induced by salidroside.
OBJECTIVE
The present study aimed to investigate whether salidroside can induce differentiation of rat mesenchymal stem cells (rMSCs) towards hepatocytes in vitro and the mechanism of hepatic differentiation of rMSCs.


METHODS
rMSCs were subject to hepatic differentiation. One, two and three weeks later, the expression of alpha fetoprotein (AFP) and albumin (ALB), cytochrome P450 (CYP450)-dependent activity and inducibility, cellular uptake of low density lipoprotein (LDL) and urea synthesis were assessed and the hepatic differentiation of rMSCs was evaluated. In order to unravel the mechanism of hepatic differentiation of rMSCs in vitro, inhibitors of extracellular regulated kinase1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI3K) and p38 were applied. When the process of hepatic differentiation was completed, special proteins of hepatic differentiation were detected and blocking of inhibitors was evaluated.


RESULTS
Salidroside significantly induce differentiation of rMSCs towards hepatocytes. Differentiated rMSCs have typical functional hepatic characteristics. The results also showed that the ERK1/2 and PI3K signalling pathways play important roles in the regulatory effects of salidroside on hepatic differentiation of rMSCs and are involved in cell fate determinations, while the p38 signalling pathway does not.


CONCLUSIONS
Salidroside can induce differentiation of rMSCs towards hepatocytes in vivo, and the ERK1/2 or PI3K signalling pathway underlie the process of hepatic differentiation.
Ouyang
Jing-Feng
JF
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Lou
Jianguo
J
Yan
Chen
C
Ren
Zi-Hua
ZH
Qiao
Hong-Xiang
HX
Hong
Dong-Sheng
DS
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D010636:Phenols / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D029771:Rhodiola / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects*
D005960:Glucosides; D010636:Phenols; D058539:Phosphatidylinositol 3-Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; C009172:rhodioloside