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

Bob Meek, Silvie Cloosen, Chiara Borsotti, Catharina H.M.J. Van Elssen, Joris Vanderlocht, Melanie C.A. Schnijderberg, Marjolein W.M. Van Der Poel, Bas Leewis, Reinout Hesselink, Markus G. Manz, Yoshimoto Katsura, Hiroshi Kawamoto, Wilfred T.V. Germeraad, Gerard M.J. Bos

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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-/- 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.

Original languageEnglish
Pages (from-to)261-264
Number of pages4
JournalBlood
Volume115
Issue number2
DOIs
Publication statusPublished - 14-01-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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