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