PMID- 12799295 OWN - NLM STAT- MEDLINE DCOM- 20030724 LR - 20190616 IS - 0077-8923 (Print) IS - 0077-8923 (Linking) VI - 996 DP - 2003 May TI - Transplanted human cord blood cells give rise to hepatocytes in engrafted mice. PG - 174-85 AB - Recent studies suggest that rodent hepatocytes may be derived from hematopoietic stem cells. In the current study, the potential hematopoietic origin of hepatocytes was addressed using xenogeneic transplantation of human cord blood cells. CD34(+) or CD45(+) human cord blood cells were transplanted into "conditioned" newborn NOD/SCID/beta2-microglobulin(null) mice. At 4 to 5 months post-transplantation, livers of the recipient mice were cryosectioned and examined for evidence of human hepatocyte engraftment using RT-PCR to detect human albumin mRNA, immunohistochemistry to detect human hepatocytic proteins, and fluorescence in situ hybridization (FISH) to detect the presence of human centromeric DNA. Analysis of the bone marrow of transplanted mice revealed that 21.0-45.9% of the cells were human CD45(+) cells. FISH analysis of frozen sections of transplanted mouse liver revealed the presence of engrafted cells positive for human centromeric DNA. That engrafted human cells functioned as hepatocytes was indicated by the expression of human albumin mRNA, as judged by RT-PCR. FISH analysis with human and mouse centromeric DNA probes excluded spontaneous cell fusion as the cause for the generation of human hepatocytes. Human cord blood cells can give rise to hepatocytes in a xenogeneic transplantation model. This model will be useful to further characterize the cord blood progenitors of hepatocytes. FAU - Ishikawa, Fumihiko AU - Ishikawa F AD - Department of Veterans Affairs Medical Center, Charleston, South Carolina 29401, USA. FAU - Drake, Christopher J AU - Drake CJ FAU - Yang, Su AU - Yang S FAU - Fleming, Paula AU - Fleming P FAU - Minamiguchi, Hitoshi AU - Minamiguchi H FAU - Visconti, Richard P AU - Visconti RP FAU - Crosby, Christopher V AU - Crosby CV FAU - Argraves, W Scott AU - Argraves WS FAU - Harada, Mine AU - Harada M FAU - Key, L Lyndon Jr AU - Key LL Jr FAU - Livingston, Anne G AU - Livingston AG FAU - Wingard, John R AU - Wingard JR FAU - Ogawa, Makio AU - Ogawa M LA - eng GR - P01-CA78582/CA/NCI NIH HHS/United States GR - R01-DK54197/DK/NIDDK NIH HHS/United States GR - R01-HL52813/HL/NHLBI NIH HHS/United States GR - R01-HL57375/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Ann N Y Acad Sci JT - Annals of the New York Academy of Sciences JID - 7506858 RN - 0 (Antigens, CD34) RN - 0 (RNA, Messenger) RN - 0 (Serum Albumin) SB - IM MH - Animals MH - Antigens, CD34/metabolism MH - Bone Marrow Cells MH - *Cell Differentiation MH - Cell Division MH - Fetal Blood/*cytology MH - Hepatocytes/*cytology MH - Humans MH - In Situ Hybridization, Fluorescence MH - Mice MH - RNA, Messenger/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Serum Albumin/genetics/metabolism MH - Transplantation, Heterologous EDAT- 2003/06/12 05:00 MHDA- 2003/07/25 05:00 CRDT- 2003/06/12 05:00 PHST- 2003/06/12 05:00 [pubmed] PHST- 2003/07/25 05:00 [medline] PHST- 2003/06/12 05:00 [entrez] AID - 10.1111/j.1749-6632.2003.tb03245.x [doi] PST - ppublish SO - Ann N Y Acad Sci. 2003 May;996:174-85. doi: 10.1111/j.1749-6632.2003.tb03245.x.