Human hepatocytes in mice receiving pre-immune injection with human cord blood cells.
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.
Turrini
Paolo
P
Pharmacology Department, Istituto di Ricerca di Biologia Molecolare "P.Angeletti", Merck Sharp and Dohme Research Laboratories, Rome, Italy.
Monego
Giovanni
G
Gonzalez
Josè
J
Cicuzza
Sandra
S
Bonanno
Giuseppina
G
Zelano
Giovanni
G
Rosenthal
Nadia
N
Paonessa
Giacomo
G
Laufer
Ralph
R
Padron
Julio
J
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*