title: Effect of hepatocyte growth factor on long term hematopoiesis of human progenitor cells in transgenic-severe combined immunodeficiency mice.
abstract: Hepatocyte growth factor (HGF), which was originally isolated as a liver generating factor, enhances hematopoiesis. To study the effect of HGF on hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs), we generated severe combined immunodeficiency (SCID) mice producing human (h) HGF and/or stem cell factor (SCF) by transferring the relevant genes to fertilized eggs, and then transplanted hematopoietic progenitors from human cord blood into the transgenic (Tg) SCID mice. Six months after transplantation, a significantly larger number of human cells were found in the Tg SCID mice than in non-Tg controls. Characteristically, the recipient SCID mice producing h HGF (HGF-SCID) had a significantly increased number of h CD41+ cells, whereas the SCF-SCID recipients had more CD11b+ cells. Significantly large numbers of CD34+ progenitors were found in the SCID mice transferred with both h HGF and h SCF genes (HGF/SCF-SCID) when compared with HGF-SCID or SCF-SCID mice. These results imply that HGF supports the differentiation of progenitors in megakaryocyte lineage, whereas SCF supports that in myeloid lineage. The results also imply that HGF acts on HSCs/HPCs as a synergistic proliferative factor combined with SCF. We have demonstrated the advantage of the human cytokine-producing animal in the maintenance of human HSCs.
authors.affiliation: Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai City, Osaka, Japan. sugiura@vet.osakafu-u.ac.jp
authors.forename: Kikuya
authors.initials: K
authors.lastname: Sugiura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Taketani
authors.forename: Tomoo
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Nishino
authors.forename: Naoki
authors.initials: N
authors.lastname: Nishino
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Fujisawa
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hisha
authors.forename: Toshio
authors.initials: T
authors.lastname: Inaba
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D019556:COS Cells; D002522:Chlorocebus aethiops; D005260:Female; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D019089:Stem Cell Factor / Q000502:physiology
chemical_list: D018952:Antigens, CD34; D019089:Stem Cell Factor; D017228:Hepatocyte Growth Factor; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human