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.
- SourceAvailable from: Tobias Cantz
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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. "
ABSTRACT: The liver has adapted to the inflow of ingested toxins by the evolutionary development of unique regenerative properties and responds to injury or tissue loss by the rapid division of mature cells. Proliferation of the parenchymal cells, i.e. hepatocytes and epithelial cells of the bile duct, is regulated by numerous cytokine/growth-factor-mediated pathways and is synchronised with extracellular matrix degradation and restoration of the vasculature. Resident hepatic stem/progenitor cells have also been identified in small numbers in normal liver and implicated in liver tissue repair. Their putative role in the physiology, pathophysiology and therapy of the liver, however, is not yet precisely known. Hepatic stem/progenitor cells also known as "oval cells" in rodents have been implicated in liver tissue repair, at a time when the capacity for hepatocyte and bile duct replication is exhausted or experimentally inhibited (facultative stem/progenitor cell pool). Although much more has to be learned about the role of stem/progenitor cells in the physiology and pathophysiology of the liver, experimental analysis of the therapeutic value of these cells has been initiated. Transplantation of hepatic stem/progenitor cells or in vivo pharmacological activation of the pool of hepatic stem cells may provide novel modalities for the therapy of liver diseases. In addition, extrahepatic stem cells (e.g. bone marrow cells) are being investigated for their contribution to liver regeneration. Hepatic progenitor cells derived from embryonic stem cells are included in this review, which also discusses future perspectives of stem cell-based therapies for liver diseases.Cell and Tissue Research 02/2008; 331(1):271-82. DOI:10.1007/s00441-007-0483-6 · 3.33 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  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. "
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 · 10.40 Impact Factor
Conference Paper: A synthesis of fuzzy control surfaces in CMOS technology[Show abstract] [Hide abstract]
ABSTRACT: A new design of a monolithic CMOS analog function synthesizer based on current-mode techniques is presented together with its application to fuzzy logic controllers. The system fuzzy control strategy has previously been simulated, thus obtaining the control surface which is then approximated by planes. The integrated circuit realizes the implicit equation of each plane whose coefficients are previously introduced in a static RAM memory. The approximated control surface allows us to obtain the control action directly. This controller is specially adequate to control systems where the fast response in control loop is necessary. The simulation shows that the maximum propagation delay (from a step change in the inputs) is 200 nsec. To illustrate the use of this circuit this controller is applied to control a DC-DC switching regulatorFuzzy Systems, 1997., Proceedings of the Sixth IEEE International Conference on; 08/1997