Use of Thymidine Kinase Recombinant Adenovirus and Ganciclovir Mediated Mouse Liver Preconditioning for Hepatocyte Xenotransplantation

• Published in: Methods in molecular biology (Clifton, N.J.) Vol. 1506; p. 179
• Main Authors: Moreno, Daniel, Neri, Leire, Vicente, Eva, Vales, Africa, Aldabe, Rafael
• Format: Journal Article
• Language: English
• Published: United States 2017
• Subjects: Adenoviridae - genetics; Animals; Cell Separation - methods; Cell Transplantation - adverse effects; Cell Transplantation - instrumentation; Cell Transplantation - methods; Chemical and Drug Induced Liver Injury, Chronic; Disease Models, Animal; Ganciclovir - toxicity; HEK293 Cells; Hepatocytes - transplantation; Humans; Liver - physiology; Liver Regeneration - drug effects; Male; Mice; Mice, Inbred BALB C; Simplexvirus - genetics; Thymidine Kinase - genetics; Transduction, Genetic - methods; Transplantation Chimera - physiology; Transplantation Chimera - surgery; Transplantation Conditioning - methods; Transplantation, Heterologous - adverse effects; Transplantation, Heterologous - methods; Viral Nonstructural Proteins - genetics; Thymidine kinase; Ganciclovir; Xenograft; Sinusoidal cells; Adenovirus; Chimeric liver
• DOI: 10.1007/978-1-4939-6506-9_12

Hepatocyte transplantation is the best approach to maintain and propagate differentiated hepatocytes from different species. Host liver has to be adapted for transplanted hepatocytes productive engraftment and proliferation being required a chronic liver injury to eliminate host hepatocytes and provide a proliferative advantage to the transplanted hepatocytes. Most valuable mouse models for xenograft hepatocyte transplantation are based on genetically modified animals to cause a chronic liver damage and to limit host hepatocyte regeneration potential. We present a methodology that generates a chronic liver damage and can be applied to any host mouse strain and animal species based on the inoculation of a recombinant adenovirus to express herpes simplex thymidine kinase in host hepatocytes sensitizing them to ganciclovir treatment. This causes a prolonged liver damage that allows hepatocyte transplantation and generation of regenerative nodules in recipient mouse liver integrated by transplanted cells and host sinusoidal. Obtained chimeric animals maintain functional chimeric nodules for several weeks, ready to be used in any study.