Homogeneous differentiation of hepatocyte-like cells from embryonic stem cells: applications for the treatment of liver failure.
One of the major hurdles of cellular therapies for the treatment of liver failure is the low availability of functional human hepatocytes. While embryonic stem (ES) cells represent a potential cell source for therapy, current methods for differentiation result in mixed cell populations or low yields of the cells of interest. Here we describe a rapid, direct differentiation method that yields a homogeneous population of endoderm-like cells with 95% purity. Mouse ES cells cultured on top of collagen-sandwiched hepatocytes differentiated and proliferated into a uniform and homogeneous cell population of endoderm-like cells. The endoderm-like cell population was positive for Foxa2, Sox17, and AFP and could be further differentiated into hepatocyte-like cells, demonstrating hepatic morphology, functionality, and gene and protein expression. Incorporating the hepatocyte-like cells into a bioartificial liver device to treat fulminant hepatic failure improved animal survival, thereby underscoring the therapeutic potential of these cells.
Cho
Cheul H
CH
Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Parashurama
Natesh
N
Park
Eric Y H
EY
Suganuma
Kazuhiro
K
Nahmias
Yaakov
Y
Park
Jaesung
J
Tilles
Arno W
AW
Berthiaume
François
F
Yarmush
Martin L
ML
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology*; D005260:Female; D022781:Hepatocytes / Q000166:cytology*; D008107:Liver Diseases / Q000628:therapy*; D008115:Liver Regeneration; D019164:Liver, Artificial; D008297:Male; D051379:Mice; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley