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 α-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. [Copyright &y& Elsevier]