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Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution

Delaney, Colleen and Heimfeld, Shelly and Brashem-Stein, Carolyn and Voorhies, Howard and Manger, Ronald and Bernstein, Irwin (2010) Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nature Medicine, 16 (2). pp. 232-236. ISSN 1546-170X

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Article URL: http://www.nature.com/nm/journal/v16/n2/abs/nm.208...

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.

Item Type: Article
Additional Information: This article is available to subscribers only via the URL above for the first six months following publication.
DOI: 10.1038/nm.2080
PubMed ID: 20081862
NIHMSID: NIHMS173311
PMCID: PMC2819359
Grant Numbers: R24 HL74445, K23 HL077446, K12 CA076930, 5R01HL080245-02, CA15704, DK56465
Keywords or MeSH Headings: * Adolescent * Adult * Animals * Bone Marrow Cells/cytology* * Child * Child, Preschool * Fetal Blood/cytology* * Humans * Mice * Mice, Inbred NOD * Mice, SCID * Receptors, Notch/physiology* * Stem Cells/cytology* * Young Adult
Depositing User: Library Staff
Date Deposited: 22 Feb 2010 20:30
Last Modified: 14 Feb 2012 14:43
URI: http://authors.fhcrc.org/id/eprint/354

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