| US 7,473,555 B2 | ||
| Protocols for making hepatocytes from embryonic stem cells | ||
| Ramkumar Mandalam, Union City, Calif. (US); Saadia Faouzi, Daly City, Calif. (US); Isabelle Nadeau, San Francisco, Calif. (US); Kristina Pfendler-Bonham, South San Francisco, Calif. (US); Namitha Rao, San Jose, Calif. (US); Melissa K. Carpenter, London (Canada); Lakshmi Rambhatla, Redwood City, Calif. (US); and Choy-Pik Chiu, Cupertino, Calif. (US) | ||
| Assigned to Geron Corporation, Menlo Park, Calif. (US) | ||
| Filed on Mar. 26, 2004, as Appl. No. 10/810,311. | ||
| Application 10/810311 is a continuation in part of application No. 10/087142, filed on Mar. 01, 2002, granted, now 7,282,366. | ||
| Application 10/087142 is a continuation in part of application No. 10/001267, filed on Oct. 31, 2001, granted, now 7,256,042. | ||
| Application 10/001267 is a continuation in part of application No. 09/872182, filed on May 31, 2001, granted, now 6,506,574. | ||
| Application 09/872182 is a continuation in part of application No. PCT/US01/13471, filed on Apr. 26, 2001. | ||
| Claims priority of provisional application 60/200095, filed on Apr. 27, 2000. | ||
| Prior Publication US 2005/0037493 A1, Feb. 17, 2005 | ||
| This patent is subject to a terminal disclaimer. | ||
| Int. Cl. C12N 5/00 (2006.01); C12N 5/02 (2006.01); C12N 5/08 (2006.01) | ||
| U.S. Cl. 435—377 [435/366; 435/370] | 20 Claims |
| 1. A process for differentiating primate pluripotent stem (pPS) cells into mature hepatocytes in at least three discrete steps,
comprising:
a) culturing undifferentiated pPS cells under conditions which cause differentiation of the cells into cells having characteristics
of fetal endoderm;
b) culturing the cells from a) under conditions which cause differentiation of fetal endoderm cells into cells having characteristics
of hepatocyte progenitor cells;
c) culturing the cells from b) under conditions which cause differentiation of hepatocyte progenitor cells into cells having
characteristics of mature hepatocytes;
thereby producing a cell population that has at least five of the following characteristics: antibody-detectable expression
of α1-antitrypsin (AAT);
antibody-detectable expression of albumin;
absence of antibody-detectable expression of a-fetoprotein;
RT-PCR detectable expression of asialoglycoprotein receptor (ASGR);
evidence of glycogen storage;
evidence of cytochrome p450 enzyme activity;
evidence of glucose-6-phosphatase enzyme activity; and
the morphological features of hepatocytes.
|