Human hepatocytes in mice receiving pre-immune injection with human cord blood cells

Pharmacology Department, Istituto di Ricerca di Biologia Molecolare "P.Angeletti", Merck Sharp and Dohme Research Laboratories, Rome, Italy.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 02/2005; 326(1):66-73. DOI: 10.1016/j.bbrc.2004.10.204
Source: PubMed


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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    • "Some researchers have argued that stem cells derived from bone marrow or cord blood of human origin exhibit higher plasticity than the respective mouse or rat cells (Di Campli et al. 2004; Ishikawa et al. 2003; Kakinuma et al. 2003; Newsome et al. 2003; Tanabe et al. 2004; Turrini et al. 2005; Wang et al. 2003a). Indeed, several groups have detected high rates of human hepatocyte formation without signs of fusion in xenogenic murine transplantation models. "
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    Cell and Tissue Research 02/2008; 331(1):271-82. DOI:10.1007/s00441-007-0483-6 · 3.57 Impact Factor
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    • "CD34 + cells isolated from cord blood 3–5 · 10 5 for intra-fetal and 15–20 cells for intrablastocyst injection None Expression of human albumin, HepPar1 antigen, and human a1-antitrypsin (IHC, RT-PCR) 1 and 4 weeks after birth m [72] ulated a relatively large number of independent groups to study the fate of different types of human stem and precursor cells in livers of experimental animals (Table 2). Without doubt differentiation of human stem cells to genuine hepatocytes or even to liver tissue would be an enormous progress with high clinical relevance. "
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    ABSTRACT: In recent years the interest in liver cell therapy has been increasing continuously, since the demand for whole liver transplantations in human beings far outweighs the supply. From the clinical point of view, transplantation of hepatocytes or hepatocyte-like cells may represent an alternative to orthotopic liver transplants in acute liver failure, for the correction of genetic disorders resulting in metabolically deficient states, and for late stage liver disease such as cirrhosis. Although the concept of cell therapy for various diseases of the liver is widely accepted, the practical approach in humans often remains difficult. An international expert panel critically discussed the recent published data on clinical and experimental hepatocyte transplantation and the possible role of stem cells in liver tissue repair. This paper aims to summarise the present status of cell based therapies for liver diseases and to identify areas of future preclinical and clinical research.
    Journal of Hepatology 08/2006; 45(1):144-59. DOI:10.1016/j.jhep.2006.04.002 · 11.34 Impact Factor
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