TY - JOUR
T1 - In vitro-differentiated T/natural killer-cell progenitors derived from human CD34+ cells mature in the thymus
AU - Meek, Bob
AU - Cloosen, Silvie
AU - Borsotti, Chiara
AU - Van Elssen, Catharina H.M.J.
AU - Vanderlocht, Joris
AU - Schnijderberg, Melanie C.A.
AU - Van Der Poel, Marjolein W.M.
AU - Leewis, Bas
AU - Hesselink, Reinout
AU - Manz, Markus G.
AU - Katsura, Yoshimoto
AU - Kawamoto, Hiroshi
AU - Germeraad, Wilfred T.V.
AU - Bos, Gerard M.J.
PY - 2010/1/14
Y1 - 2010/1/14
N2 - 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-/- γc-/- mice, these cells selectively home to the thymus and differentiate toward surface T-cell receptor- αβ+ 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.
AB - 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-/- γc-/- mice, these cells selectively home to the thymus and differentiate toward surface T-cell receptor- αβ+ 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.
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U2 - 10.1182/blood-2009-05-223990
DO - 10.1182/blood-2009-05-223990
M3 - Article
C2 - 19828700
AN - SCOPUS:75649127674
SN - 0006-4971
VL - 115
SP - 261
EP - 264
JO - Blood
JF - Blood
IS - 2
ER -