Repopulation of adult and neonatal mice with human hepatocytes: A chimeric animal model

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 51; pp. 20507 - 20511
• Main Authors: Bissig, Karl-Dimiter, Le, Tam T, Woods, Niels-Bjarne, Verma, Inder M
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18.12.2007; National Acad Sciences
• Subjects: Adults; Albumins; Animal models; Animals; Biological Sciences; Cell fusion; Cells; Chimera; Gene expression; Green Fluorescent Proteins - analysis; Green Fluorescent Proteins - genetics; Hepatocytes; Hepatocytes - cytology; Hepatocytes - transplantation; Humans; Hydrolases - genetics; Immune Tolerance - genetics; Liver; Mice; Models, Animal; Rodents; Transgenes; Transplantation; Transplantation, Heterologous - methods; Transplants & implants
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0710528105

We report the successful transplantation of human hepatocytes in immunodeficient, fumarylacetoacetate hydrolase-deficient (fah⁻/⁻) mice. Engraftment occurs over the entire liver acinus upon transplantation. A few weeks after transplantation, increasing concentrations of human proteins (e.g., human albumin and human C3a) can be measured in the blood of the recipient mouse. No fusion between mouse and human hepatocytes can be detected. Three months after transplantation, up to 20% of the mouse liver is repopulated by human hepatocytes, and sustained expression of lentiviral vector transduced gene can be observed. We further report the development of a hepatocyte transplantation method involving a transcutaneous, intrahepatic injection in neonatal mice. Human hepatocytes engraft over the entire injected lobe with an expansion pattern similar to those observed with intrasplenic transplantation.