Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-29249
Meek, B; Cloosen, S; Borsotti, C; Van Elssen, C H; Vanderlocht, J; Schnijderberg, M C; van der Poel, M W; Leewis, B; Hesselink, R; Manz, M G; Katsura, Y; Kawamoto, H; Germeraad, W T; Bos, G M (2010). In vitro-differentiated T/natural killer-cell progenitors derived from human CD34+ cells mature in the thymus. Blood, 115(2):261-265.
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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Hematology|
|DDC:||610 Medicine & health|
|Deposited On:||02 Mar 2010 14:41|
|Last Modified:||28 Nov 2013 00:52|
|Publisher:||American Society of Hematology|
|Citations:||Web of Science®. Times cited: 12|
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