title: Expansion of haematopoietic stem cells from normal donors and bone marrow failure patients by recombinant hoxb4.
abstract: In this study six versions of recombinant human hoxb4 proteins were produced and their effectiveness evaluated in expanding human haematopoietic stem and progenitor cells in vitro and in vivo. An N-terminal-tat and C-terminal histidine-tagged version of hoxb4 (T-hoxb4-H) showed the highest activity in expanding colony forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs) when used at 50 nmol/l concentration in cell culture. Human cord blood CD34(+) cells cultured with 50 nmol/l T-hoxb4-H showed a significant increase in severe-combined immunodeficient mouse-repopulating cells (SRCs). In a mouse model of immune-mediated bone marrow (BM) failure, T-hoxb4-H showed an additive effect with cyclosporine in alleviating pancytopenia. In addition, T-hoxb4-H expanded CFC and LTC-IC on BM samples from patients with refractory severe aplastic anaemia and myelodysplastic syndromes: after culturing with 50 nmol/l T-hoxb4-H for 4 d, BM cells from 10 of the 11 patients showed increases in CFC and LTC-IC, and the increase in LTC-IC was statistically significant in samples from four patients. Recombinant human hoxb4 could be a promising therapeutic agent for BM failure.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892-1202, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.forename: Jichun
authors.initials: J
authors.lastname: Chen
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000741:Anemia, Aplastic / Q000188:drug therapy / Q000473:pathology*; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004359:Drug Therapy, Combination; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D018398:Homeodomain Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D051379:Mice; D016513:Mice, SCID; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014157:Transcription Factors / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018952:Antigens, CD34; C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D014157:Transcription Factors; D016572:Cyclosporine