title: Human hepatocytes in mice receiving pre-immune injection with human cord blood cells.
abstract: It is well established that certain subpopulations of human adult stem cells can generate hepatocyte-like cells when transplanted into adult immunosuppressed mice. In the present study, we wanted to explore whether xeno-transplantation of human cord blood CD34(+) (hCBCD34(+)) cells during pre-immune stages of development in immunocompetent mice might also lead to human-mouse liver chimerism. Freshly isolated hCBCD34(+) cells were xeno-transplanted into non-immunosuppressed mice by both intra-blastocyst and intra-fetal injections. One and four weeks after birth, immunostaining for different human-specific hepatocyte markers: human hepatocyte-specific antigen, human serum albumin, and human alpha-1-antitrypsin indicated the presence of human hepatocyte-like cells in the livers of transplanted animals. Detection of human albumin mRNA further corroborated the development of pre-immune human-mouse chimeras. The current report, besides providing new evidence of the potential of hCBCD34(+) cells to generate human hepatocyte-like cells, suggests novel strategies for generating immunocompetent mice harboring humanized liver.
authors.affiliation: Pharmacology Department, Istituto di Ricerca di Biologia Molecolare "P.Angeletti", Merck Sharp and Dohme Research Laboratories, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Turrini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Monego
authors.forename: Josè
authors.initials: J
authors.lastname: Gonzalez
authors.forename: Sandra
authors.initials: S
authors.lastname: Cicuzza
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Bonanno
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zelano
authors.forename: Nadia
authors.initials: N
authors.lastname: Rosenthal
authors.forename: Giacomo
authors.initials: G
authors.lastname: Paonessa
authors.forename: Ralph
authors.initials: R
authors.lastname: Laufer
authors.forename: Julio
authors.initials: J
authors.lastname: Padron
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005260:Female; D022781:Hepatocytes / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D007121:Immunocompetence / Q000502:physiology; D007267:Injections / Q000379:methods; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D051379:Mice; D016513:Mice, SCID; D011247:Pregnancy; D013234:Stem Cells / Q000166:cytology*; D014183:Transplantation, Heterologous / Q000379:methods*