In vitro-differentiated T/natural killer-cell progenitors derived from human CD34+ cells mature in the thymus.

Abstract:

:Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a treatment option for patients with hematopoietic malignancies that is hampered by treatment-related morbidity and mortality, in part the result of opportunistic infections, a direct consequence of delayed T-cell recovery. Thymic output can be improved by facilitation of thymic immigration, known to require precommitment of CD34(+) cells. We demonstrate that Delta-like ligand-mediated predifferentiation of mobilized CD34(+) cells in vitro results in a population of thymocyte-like cells arrested at a T/natural killer (NK)-cell progenitor stage. On intrahepatic transfer to Rag2(-/-)gamma(c)(-/-) mice, these cells selectively home to the thymus and differentiate toward surface T-cell receptor-alphabeta(+) mature T cells considerably faster than animals transplanted with noncultured CD34(+) cells. This finding creates the opportunity to develop an early T-cell reconstitution therapy to combine with HSCT.

journal_name

Blood

journal_title

Blood

authors

Meek B,Cloosen S,Borsotti C,Van Elssen CH,Vanderlocht J,Schnijderberg MC,van der Poel MW,Leewis B,Hesselink R,Manz MG,Katsura Y,Kawamoto H,Germeraad WT,Bos GM

doi

10.1182/blood-2009-05-223990

subject

Has Abstract

pub_date

2010-01-14 00:00:00

pages

261-4

issue

2

eissn

0006-4971

issn

1528-0020

pii

blood-2009-05-223990

journal_volume

115

pub_type

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