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Human cord blood stem cells generate human cytokeratin 18-negative hepatocyte-like cells in injured mouse liver

Item Type:Article
Title:Human cord blood stem cells generate human cytokeratin 18-negative hepatocyte-like cells in injured mouse liver
Creators Name:Sharma, A.D. and Cantz, T. and Richter, R. and Eckert, K. and Henschler, R. and Wilkens, L. and Jochheim-Richter, A. and Arseniev, L. and Ott, M.
Abstract:Differentiation of adult bone marrow (BM) cells into nonhematopoietic cells is a rare phenomenon. Several reports, however, suggest that human umbilical cord blood (hUCB)-derived cells give rise to hepatocytes after transplantation into nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice. Therefore, we analyzed the hepatic differentiation potential of hUCB cells and compared the frequency of newly formed hepatocyte-like cells in the livers of recipient NOD-SCID mice after transplantation of hUCB versus murine BM cells. Mononuclear cell preparations of hUCB cells or murine BM from enhanced green fluorescent protein transgenic or wild-type mice were transplanted into sublethally irradiated NOD-SCID mice. liver regeneration was induced by carbon tetracliloride injury with and without subsequent hepatocyte growth factor treatment. By immunohistocltemistry and reverse transcriptase-polymerase chain reaction, we detected clusters of hepatocyte-like cells in the livers of hUCB-transplanted mice. These cells expressed human albumin and Hep Par 1 but mouse CK18, suggesting the formation of chimeric hepatocyte-like cells. Native fluorescence microscopy and double immunofluorescence failed to detect single hepatocytes derived from transplanted enhanced green fluorescent protein-transgenic mouse BM. Fluorescent in situ hybridization rarely revealed donor-derived hepatocyte-like cells after cross-gender mouse BM transplantation. Thus, hUCB cells have differentiation capabilities different from murine BM cells after transplantation into NOD-SCID mice, demonstrating the importance of further testing before hUCB cells can be used therapeutically.
Keywords:Bone Marrow Cells, Bone Marrow Transplantation, Carbon Tetrachloride, Cell Differentiation, Cord Blood Stem Cell Transplantation, Fetal Blood, Green Fluorescent Proteins, Hematopoietic Stem Cells, Hepatocyte Growth Factor, Hepatocytes, Heterologous Transplantation, Inbred C57BL Mice, Inbred NOD Mice, Keratins, Liver, Liver Regeneration, SCID Mice, Animals, Mice
Source:American Journal of Pathology
Publisher:American Society for Investigative Pathology
Page Range:555-564
Date:1 August 2005
Official Publication:http://ajp.amjpathol.org/cgi/content/abstract/167/2/555
PubMed:View item in PubMed

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