Hepatic differentiation of rat mesenchymal stem cells by a small molecule.
Mesenchymal stem cells (MSCs) are capable of self-renewal and multilineage differentiation. A periodic acid-Schiff (PAS) stain-based assay was developed to screen for small-molecule inducers of hepatic differentiation of bone marrow MSCs. 2-(4-Bromophenyl)-N-(4-fluorophenyl)-3-propyl-3H-imidazo[4,5-b]pyridin-5-amine (SJA710-6) was identified as a novel small molecule able to induce the differentiation of rat MSCs (rMSCs) toward hepatocyte-like cells in vitro, where rMSCs treated with SJA710-6 have typical morphological and functional characteristics of hepatic cells, including glycogen storage, urea secretion, uptake of low density lipoprotein (LDL) and expression of hepatocyte-specific genes and proteins. Expression of FoxH1 (FAST1/2) induces the differentiation of rMSCs towards hepatocyte-like cells, suggesting that this gene plays an important role in the hepatic fate specification of rMSCs.
Institute of Materia Medica, College of Pharmaceutical Sciences, Zhejiang University, 866 YuHangTang Road, Hangzhou, 310058, China.
Jingfeng
J
Ouyang
Jiaan
J
Shao
Hongbin
H
Zou
Yijia
Y
Lou
Yongping
Y
Yu
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism; D014508:Urea / Q000378:metabolism
C576502:2-(4-bromophenyl)-N-(4-fluorophenyl)-3-propyl-3H-imidazo(4,5-b)pyridin-5-amine; D051858:Forkhead Transcription Factors; D007093:Imidazoles; D008077:Lipoproteins, LDL; D011725:Pyridines; D012709:Serum Albumin; D014508:Urea; D006003:Glycogen