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

Pubmed ID: 20081862

Pubmed Central ID: PMC2819359

Journal: Nature medicine

Publication Date: Feb. 1, 2010

Affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

MeSH Terms: Humans, Adult, Adolescent, Young Adult, Child, Animals, Fetal Blood, Mice, Mice, SCID, Stem Cells, Child, Preschool, Bone Marrow Cells, Mice, Inbred NOD, Receptors, Notch

Grants: P30 DK056465, R24 HL074445, R24 HL74445, 5R01HL080245-02, CA15704, DK56465, K12 CA076930, K12 CA076930-11, K23 HL077446, K23 HL077446-05, P30 CA015704-35, P30 DK056465-119001, R01 HL080245, R01 HL080245-04, R24 HL074445-05, P30 CA015704

Authors: Delaney C, Brashem-Stein C, Bernstein ID, Heimfeld S, Voorhies H, Manger RL

Cite As: Delaney C, Heimfeld S, Brashem-Stein C, Voorhies H, Manger RL, Bernstein ID. Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat Med 2010 Feb;16(2):232-6. Epub 2010 Jan 17.

Studies:

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.