Rat hepatocyte engraftment in severe combined immunodeficient × beige mice using mouse‐specific anti‐fas antibody

Abstract

This novel model represents a simple and robust system of xenogeneic hepatocyte transplantation that could be applied to studies of liver biology, regeneration and hepatocyte transplantation.

Hepatitis B Virus Infection and Immunopathogenesis in a Humanized Mouse Model: Induction of Human-Specific Liver Fibrosis and M2-Like Macrophages

“…We confirmed the specie-specificity of Jo2 antibody [32] by incubating human liver cell line (HepG2) with Jo2 antibody. Jo2 antibody did not stain the human hCD95+ hepatocyte cell line (Figure S1A).…”

“…However, these mice have disadvantages including neonatal death, poor health and, most importantly, the lack of a human immune system [19]. To overcome these deficiencies, the A2/NSG/Fas-humanized mouse model enables inducible depletion of murine hepatocytes through the Fas apoptotic signaling pathway, resulting in elevated human liver repopulation in mice transplanted with human liver progenitor and hematopoietic stem cells [32], [33], [34], [36], [51]. Additionally, the A2/NSG background permits highly efficient engraftment and development of human xenografts including human hematopoietic stem cells compared to current immunodeficient mouse models [52].…”

“…Furthermore, the A2/NSG mouse carries the human HLA-A2 transgene, which enhances development of human MHC-restrict T lymphocytes [30]. To promote human liver cell repopulation, A2/NSG-hu HSC/Hep mice were treated with a murine specific anti-Fas agonistic antibody (Jo2) [32], [33], [34], [35], [36]. The A2/NSG-hu HSC/Hep mouse model enabled human liver and immune system development and supported long-term HBV infection, anti-HBV human immune response and HBV-induced liver diseases including hepatitis and fibrosis.…”

Xenotransplantation Literature Update January–February, 2006

“…Wilson et al [9] studied engraftment of rat hepatocytes transplanted into livers of severe combined immunodeficient (SCID) × beige hybrid mice following induction of mouse hepatocyte apoptosis using a specific anti‐mouse agonistic Fas monoclonal antibody. They observed that mice with engraftment of rat hepatocytes of >50% were protected from Fas‐mediated liver hemorrhage and hepatocyte apoptosis, and did not show an increase in liver enzymes after administration of anti‐mouse agonistic Fas monoclonal antibody.…”