Differentiation of bone marrow-derived mesenchymal stem cells into hepatocyte-like cells in an alginate scaffold.
OBJECTIVE
Alginate scaffolds are the most frequently investigated biomaterials in tissue engineering. Tissue engineering techniques that generate liver tissue have become important for treatment of a number of liver diseases and recent studies indicate that bone marrow-derived stem cells (BMSCs) can differentiate into hepatocyte-like cells. The goal of the study described here, was to examine in vitro hepatic differentiation potential of BMSCs cultured in an alginate scaffold.


METHODS
To investigate the potential of BMSCs to differentiate into hepatocyte-like cells, we cultured BMSCs in alginate scaffolds in the presence of specific growth factors including hepatocyte growth factor, epidermal growth factor and fibroblast growth factor-4.


RESULTS
We can demonstrate that alginate scaffolds are compatible for growth of BMSCs and when cultured in alginate scaffolds for several days they display several liver-specific markers and functions. Specifically, they expressed genes encoding alpha-foetoprotein, albumin (ALB), connexin 32 and CYP7A1. In addition, these BMSCs produced both ALB and urea, expressed cytokeratin-18 (CK-18) and were capable of glycogen storage. Percentage of CK-18 positive cells, a marker of hepatocytes, was 56.7%.


CONCLUSIONS
Our three-dimensional alginate scaffolds were highly biocompatible with BMSCs. Furthermore, culturing induced their differentiation into hepatocyte-like cells. Therefore, BMSCs cultured in alginate scaffolds may be applicable for hepatic tissue engineering.
Lin
N
N
Department of Hepatobiliary Surgery, the Third Affiliated Hospital, Sun Yat-Sen University, GuangZhou, China.
Lin
J
J
Bo
L
L
Weidong
P
P
Chen
S
S
Xu
R
R
D000418:Albumins / Q000378:metabolism; D000464:Alginates / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000008:administration & dosage; D051519:Fibroblast Growth Factor 4 / Q000008:administration & dosage; D020723:Glucuronic Acid / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage; D022781:Hepatocytes / Q000166:cytology*; D006603:Hexuronic Acids / Q000378:metabolism; D053538:Keratin-18 / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054457:Tissue Scaffolds; D014508:Urea / Q000378:metabolism
D000418:Albumins; D000464:Alginates; D001672:Biocompatible Materials; D051519:Fibroblast Growth Factor 4; D006603:Hexuronic Acids; D053538:Keratin-18; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D020723:Glucuronic Acid; D014508:Urea; D006003:Glycogen