title: Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution.
abstract: Delayed myeloid engraftment after cord blood transplantation (CBT) is thought to result from inadequate numbers of progenitor cells in the graft and is associated with increased early transplant-related morbidity and mortality. New culture strategies that increase the number of cord blood progenitors capable of rapid myeloid engraftment after CBT would allow more widespread use of this stem cell source for transplantation. Here we report the development of a clinically relevant Notch-mediated ex vivo expansion system for human CD34(+) cord blood progenitors that results in a marked increase in the absolute number of stem/progenitor cells, including those capable of enhanced repopulation in the marrow of immunodeficient nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice. Furthermore, when cord blood progenitors expanded ex vivo in the presence of Notch ligand were infused in a clinical setting after a myeloablative preparative regimen for stem cell transplantation, the time to neutrophil recovery was substantially shortened. To our knowledge, this is the first instance of rapid engraftment derived from ex vivo expanded stem/progenitor cells in humans.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Delaney
authors.forename: Shelly
authors.initials: S
authors.lastname: Heimfeld
authors.forename: Carolyn
authors.initials: C
authors.lastname: Brashem-Stein
authors.forename: Howard
authors.initials: H
authors.lastname: Voorhies
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Manger
authors.forename: Irwin D
authors.initials: ID
authors.lastname: Bernstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002648:Child; D002675:Child, Preschool; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D051880:Receptors, Notch / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*; D055815:Young Adult
chemical_list: D051880:Receptors, Notch