Geron Corporation

Asterias Biotherapeutics, Inc.

Lakshmi Rambhatla

Melissa K Carpenter

Ramkumar Mandalam

Choy-Pik Chiu

Isabelle Nadeau

Kristina Pfendler-Bonham

Saadia Faouzi

Namitha Rao

This disclosure provides a newly developed strategy and particular options for differentiating pluripotent stem cells into cells of the hepatocyte lineage. Many of the protocols are based on a strategy in which the cells are first differentiated into early germ layer cells, then into hepatocyte precursors, and then into mature cells. The cells obtained have morphological features and phenotypic markers characteristic of human adult hepatocytes. They also show evidence of cytochrome p450 enzyme activity, validating their utility for commercial applications such as drug screening, or use in the manufacture of medicaments and medical devices for clinical therapy.

Protocols for making hepatocytes from embryonic stem cells

It has been discovered that when pluripotent stem cells are cultured in the presence of a hepatocyte differentiation agent, a population of cells is derived that has a remarkably high proportion of cells with phenotypic characteristics of liver cells. In one example, human embryonic stem cells are allowed to form embryoid bodies, and then combined with the differentiation agent n-butyrate, optionally supplemented with maturation factors. In another example, n-butyrate is added to human embryonic stem cells in feeder-free culture. Either way, a remarkably uniform cell population is obtained, which is predominated by cells with morphological features of hepatocytes, expressing surface markers characteristic of hepatocytes, and having enzymatic and biosynthetic activity important for liver function. Since stem cells readily proliferate in culture, this system provides an abundant source of cells of the hepatocyte lineage for a variety of applications, such as drug screening, and replenishing liver function in the context of clinical treatment.

Hepatocytes for therapy and drug screening made from embryonic stem cells

Process for making hepatocytes from pluripotent stem cells

Hepatocyte lineage cells derived from pluripotent stem cells

Growing community of inventors

Redwood City, CA, United States of America

Lakshmi Rambhatla