title: Dissociation of Survival, Proliferation, and State Control in Human Hematopoietic Stem Cells.
abstract: The role of growth factors (GFs) in controlling the biology of human hematopoietic stem cells (HSCs) remains limited by a lack of information concerning the individual and combined effects of GFs directly on the survival, Mitogenesis, and regenerative activity of highly purified human HSCs. We show that the initial input HSC activity of such a purified starting population of human cord blood cells can be fully maintained over a 21-day period in serum-free medium containing five GFs alone. HSC survival was partially supported by any one of these GFs, but none were essential, and different combinations of GFs variably stimulated HSC proliferation. However, serial transplantability was not detectably compromised by many conditions that reduced human HSC proliferation and/or survival. These results demonstrate the dissociated control of these three human HSC bio-responses, and set the stage for future improvements in strategies to modify and expand human HSCs ex vivo.
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, BC Cancer Research Centre, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
authors.forename: David J H F
authors.initials: DJ
authors.lastname: Knapp
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, BC Cancer Research Centre, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hammond
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, BC Cancer Research Centre, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Miller
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, BC Cancer Research Centre, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Gabrielle M
authors.initials: GM
authors.lastname: Rabu
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, BC Cancer Research Centre, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Beer
authors.affiliation: AbCellera Biologics Inc, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Marketa
authors.initials: M
authors.lastname: Ricicova
authors.affiliation: AbCellera Biologics Inc, Vancouver, BC V6T 1Z4, Canada; Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Lecault
authors.affiliation: AbCellera Biologics Inc, Vancouver, BC V6T 1Z4, Canada; Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Da Costa
authors.affiliation: Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: VanInsberghe
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, BC Cancer Research Centre, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Alice M
authors.initials: AM
authors.lastname: Cheung
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, BC Cancer Research Centre, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Davide
authors.initials: D
authors.lastname: Pellacani
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Piret
authors.affiliation: Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Carl
authors.initials: C
authors.lastname: Hansen
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, BC Cancer Research Centre, 675 West 10(th) Avenue, Vancouver, BC V5Z 1L3, Canada. Electronic address: ceaves@bccrc.ca.
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Eaves
mesh_terms: D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D039503:Integrin alpha6 / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D051379:Mice; D010641:Phenotype
chemical_list: D015415:Biomarkers; D039503:Integrin alpha6; D036341:Intercellular Signaling Peptides and Proteins
keywords: HSC; apoptosis; cell death; growth factor; hematopoietic stem cell; human; microfluidics; mitogenesis; proliferation; self-renewal; survival; transplantation; xenotransplantation