title: Fractionation of Gene Modified Hematopoietic Autografts into Multiple Weekly Infusions Does Not Improve Engraftment in Unconditioned Canine Recipients.
abstract: Hematopoietic stem cell (HSC) gene therapy will require efficient transfer of genes to HSCs and long term engraftment and proliferation of genetically modified HSCs following adoptive transfer. We evaluated whether fractionation of grafts into 4-5 weekly infusions to non-myeloablated, autologous canine recipients would improve engraftment of genetically modified HSCs. Experimental animals and controls receiving a single infusion had similar levels of engraftment with ∼3-10% of marrow derived progenitors carrying transgene sequences for up to 29 months. There appears to be no improvement of engraftment of genetically modified HSCs in non-myeloablated large animal recipients by dose fractionation.
authors.affiliation: a Department of Laboratory Medicine , Sunnybrook and Women's College Health Sciences Centre, Faculty of Medicine University of Toronto , Ontario , Canada.|b Department of Laboratory Medicine and Pathobiology , Faculty of Medicine University of Toronto , Ontario , Canada.
authors.forename: C
authors.initials: C
authors.lastname: Lutzko
authors.affiliation: c Department of Clinical Studies , Ontario Veterinary College, University of Guelph , Guelph , Ontario , Canada.
authors.forename: A C
authors.initials: AC
authors.lastname: Abrams-Ogg
authors.affiliation: a Department of Laboratory Medicine , Sunnybrook and Women's College Health Sciences Centre, Faculty of Medicine University of Toronto , Ontario , Canada.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: a Department of Laboratory Medicine , Sunnybrook and Women's College Health Sciences Centre, Faculty of Medicine University of Toronto , Ontario , Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: c Department of Clinical Studies , Ontario Veterinary College, University of Guelph , Guelph , Ontario , Canada.
authors.forename: K
authors.initials: K
authors.lastname: Lau
authors.affiliation: c Department of Clinical Studies , Ontario Veterinary College, University of Guelph , Guelph , Ontario , Canada.
authors.forename: S
authors.initials: S
authors.lastname: Kruth
authors.affiliation: a Department of Laboratory Medicine , Sunnybrook and Women's College Health Sciences Centre, Faculty of Medicine University of Toronto , Ontario , Canada.|b Department of Laboratory Medicine and Pathobiology , Faculty of Medicine University of Toronto , Ontario , Canada.
authors.forename: I D
authors.initials: ID
authors.lastname: Dubé
keywords: Hematopoietic stem cells; bone marrow transplant; gene transfer; hematopoietic cell gene therapy; long term marrow cultures