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. PMID: 20081862 Funding information This work was supported by: NIDDK NIH HHS, United States Grant ID: P30 DK056465-119001 NCI NIH HHS, United States Grant ID: K12 CA076930 NHLBI NIH HHS, United States Grant ID: R24 HL074445 NCI NIH HHS, United States Grant ID: P30 CA015704 NHLBI NIH HHS, United States Grant ID: R24 HL074445-05 NHLBI NIH HHS, United States Grant ID: R01 HL080245-04 NHLBI NIH HHS, United States Grant ID: K23 HL077446 NHLBI NIH HHS, United States Grant ID: 5R01HL080245-02 NHLBI NIH HHS, United States Grant ID: R24 HL74445 NCI NIH HHS, United States Grant ID: P30 CA015704-35 NCI NIH HHS, United States Grant ID: CA15704 NIDDK NIH HHS, United States Grant ID: P30 DK056465 NHLBI NIH HHS, United States Grant ID: R01 HL080245 NIDDK NIH HHS, United States Grant ID: DK56465 NHLBI NIH HHS, United States Grant ID: K23 HL077446-05 NCI NIH HHS, United States Grant ID: K12 CA076930-11 More Less keyboard_arrow_down
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