title: Homogeneous differentiation of hepatocyte-like cells from embryonic stem cells: applications for the treatment of liver failure.
abstract: 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.
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Cheul H
authors.initials: CH
authors.lastname: Cho
authors.forename: Natesh
authors.initials: N
authors.lastname: Parashurama
authors.forename: Eric Y H
authors.initials: EY
authors.lastname: Park
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Suganuma
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Nahmias
authors.forename: Jaesung
authors.initials: J
authors.lastname: Park
authors.forename: Arno W
authors.initials: AW
authors.lastname: Tilles
authors.forename: François
authors.initials: F
authors.lastname: Berthiaume
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
mesh_terms: 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