title: Distinct but phenotypically heterogeneous human cell populations produce rapid recovery of platelets and neutrophils after transplantation.
abstract: Delayed recovery of mature blood cells poses a serious, expensive, and often life-threatening problem for many stem cell transplantation recipients, particularly if heavily pretreated and serving as their own donor, or having a CB transplantation as the only therapeutic option. Importantly, the different cells required to ensure a rapid, as well as a permanent, hematopoietic recovery in these patients remain poorly defined. We now show that human CB and mobilized peripheral blood (mPB) collections contain cells that produce platelets and neutrophils within 3 weeks after being transplanted into sublethally irradiated NOD/scid-IL-2Rγc-null mice. The cells responsible for these 2 outputs are similarly distributed between the aldehyde dehydrogenase-positive and -negative subsets of lineage marker-negative CB and mPB cells, but their overall frequencies vary independently in individual samples. In addition, their total numbers can be seen to be much (> 30-fold) lower in a single "average" CB transplantation compared with a single "average" mPB transplantation (normalized for a similar weight of the recipient), consistent with the published differential performance in adult patients of these 2 transplantation products. Experimental testing confirmed the clinical relevance of the surrogate xenotransplantation assay for quantifying cells with rapid platelet regenerative activity, underscoring its potential for future applications.
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Alice M S
authors.initials: AM
authors.lastname: Cheung
authors.forename: Donna
authors.initials: D
authors.lastname: Leung
authors.forename: Shabnam
authors.initials: S
authors.lastname: Rostamirad
authors.forename: Kiran
authors.initials: K
authors.lastname: Dhillon
authors.forename: Paul H
authors.initials: PH
authors.lastname: Miller
authors.forename: Radina
authors.initials: R
authors.lastname: Droumeva
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Brinkman
authors.forename: Donna
authors.initials: D
authors.lastname: Hogge
authors.forename: Denis Claude
authors.initials: DC
authors.lastname: Roy
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Eaves
mesh_terms: D000328:Adult; D000818:Animals; D001773:Blood Cells / Q000145:classification / Q000166:cytology* / Q000502:physiology*; D001792:Blood Platelets / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007231:Infant, Newborn; D007958:Leukocyte Count; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D009504:Neutrophils / Q000502:physiology*; D010641:Phenotype; D010976:Platelet Count; D014183:Transplantation, Heterologous