Generation of Human Hepatocytes

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R41DK067786-01
Agency Tracking Number: DK067786
Amount: $100,000.00
Phase: Phase I
Program: STTR
Awards Year: 2004
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (775) 328-1232
Business Contact
Phone: (775) 322-5889
Research Institution
RENO, NV, 89502
 Domestic nonprofit research organization
DESCRIPTION (provided by applicant): The goal of this project is to produce "humanized" livers in large animal models such as sheep and pigs that can serve as a reliable source of significant numbers of functional human hepatocytes. The isolated human hepatocytes and/or "humanized" livers can be used for drug toxicity studies as well as for possible clinical use in patients with liver failure. Transplantation of human bone marrow (BM) CD34+ cells from normal donors of diverse genetic background into pre-immune fetal sheep/pigs can be used to generate human liver cells for use in drug toxicity studies (the aim of the present application), and from specific patients to produce livers and/or cells autologous to the patient (future goal requiring proof-of-principle studies). Feasibility data is presented demonstrating that the transplantation of CD34+ cells from human BM, mobilized peripheral blood, and cord blood into this non-injury pre-immune fetal sheep model resulted in the robust formation of relatively large numbers of human liver cells that synthesize and secret human albumin into circulation. In this human/sheep xenograft model donor (human) hepatopoiesis persists long-term (> 2years) without apparent loss of number or function. In the phase I effort we propose to determine: 1) the optimal gestational age of the sheep fetus, and 2) the optimal concentration of human bone marrow CD34+ cells for obtaining the highest percentages of human hepatocytes. Phase II effort will focus on efficient isolation, characterization, and maintenance of human liver cells from the "humanized" liver.

* Information listed above is at the time of submission. *

Agency Micro-sites

SBA logo
Department of Agriculture logo
Department of Commerce logo
Department of Defense logo
Department of Education logo
Department of Energy logo
Department of Health and Human Services logo
Department of Homeland Security logo
Department of Transportation logo
Environmental Protection Agency logo
National Aeronautics and Space Administration logo
National Science Foundation logo
US Flag An Official Website of the United States Government