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Homogeneous differentiation of hepatocyte-like cells from embryonic stem cells: applications for the treatment of liver failure

Center for Engineering in Medicine and Department of Surgery, Massachusetts General Hospital, Harvard Medical School, and the Shriners Hospitals for Children, Boston, Massachusetts, USA

¹Correspondence: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Shriners Hospitals for Children, 51 Blossom St., Boston, MA 02114, USA. E-mail: A.W.T, arno_tilles{at}hms.harvard.edu; M.L.Y, ireis{at}sbi.org

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, C. H., Parashurama, N., Park, E. Y. H., Suganuma, K., Nahmias, Y., Park, J., Tilles, A. W., Berthiaume, F., Yarmush, M. L. Homogeneous differentiation of hepatocyte-like cells from embryonic stem cells: applications for the treatment of liver failure.

Key Words: coculture • endoderm • animal model • bioartificial liver device