title: Bone marrow transplantation concurrently reconstitutes donor liver and immune system across host species barrier in mice.
abstract: Liver immunopathologic mechanisms during hepatotropic infection, malignant transformation, and autoimmunity are still unclear. Establishing a chimeric mouse with a reconstituted liver and immune system derived from a single donor across species is critical to study regional donor immune responses in recipient liver. Using a strain of mice deficient in tyrosine catabolic enzyme fumarylacetoacetate hydrolase (fah-/-) and bone marrow transplantation (BMT), we reconstituted the donor's hepatocytes and immune cells across host species barrier. Syngeneic, allogeneic or even xenogeneic rat BMT rescued most recipient fah-/- mice against liver failure by donor BM-derived FAH+ hepatocytes. Importantly, immune system developed normally in chimeras, and the immune cells together with organ architecture were intact and functional. Thus, donor BM can across host species barrier and concurrently reconstitutes MHC-identical response between immune cells and hepatocytes, giving rise to a new simple and convenient small animal model to study donor's liver immune response in mice.
authors.affiliation: Department of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Ziping
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Department of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Xuefu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002678:Chimera; D006085:Graft Survival; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism; D007107:Immune System / Q000502:physiology*; D017093:Liver Failure / Q000209:etiology / Q000378:metabolism / Q000628:therapy; D008111:Liver Function Tests; D008115:Liver Regeneration; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D051381:Rats; D012038:Regeneration; D014019:Tissue Donors; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: D006867:Hydrolases; C020156:fumarylacetoacetase