title: Ex vivo treatment of proliferating human cord blood stem cells with stroma-derived factor-1 enhances their ability to engraft NOD/SCID mice.
abstract: Ex vivo proliferation of hematopoietic stem cells (HSCs) is important for cellular and gene therapy but is limited by the observation that HSCs do not engraft as they transit S/G(2)/M. Recently identified candidate inhibitors of human HSC cycling are transforming growth factor-beta(1) (TGF-beta(1)) and stroma-derived factor-1 (SDF-1). To determine the ability of these factors to alter the transplantability of human HSCs proliferating in vitro, lin(-) cord blood cells were first cultured for 96 hours in serum-free medium containing Flt3 ligand, Steel factor, interleukin-3, interleukin-6, and granulocyte colony-stimulating factor. These cells were then transferred to medium containing Steel factor and thrombopoietin with or without SDF-1 and/or TGF-beta(1) for 48 hours. Exposure to SDF-1 but not TGF-beta(1) significantly increased (> 2-fold) the recovery of HSCs able to repopulate nonobese diabetic/severe combined immunodeficiency mice. These results suggest new strategies for improving the engraftment activity of HSCs stimulated to proliferate ex vivo.
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, University of British Columbia, Vancouver, Canada.
authors.forename: Hanno
authors.initials: H
authors.lastname: Glimm
authors.forename: Patrick
authors.initials: P
authors.lastname: Tang
authors.forename: Ian
authors.initials: I
authors.lastname: Clark-Lewis
authors.forename: Christof
authors.initials: C
authors.lastname: von Kalle
authors.forename: Connie
authors.initials: C
authors.lastname: Eaves
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology; D006085:Graft Survival / Q000187:drug effects*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D016688:Mice, Inbred NOD / Q000502:physiology*; D016513:Mice, SCID / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D003470:Culture Media; C515256:Cxcl12 protein, mouse; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1