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

doi:10.1182/blood-2009-05-223990

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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-alpha beta(+) 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. ( Blood. 2010; 115:261-264)

Original language	English
Pages (from-to)	261-264
Journal	Blood
Volume	115
Issue number	2
DOIs	https://doi.org/10.1182/blood-2009-05-223990
Publication status	Published - 14 Jan 2010

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10.1182/blood-2009-05-223990

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Meek, B., Cloosen, S., Borsotti, C., Van Elssen, C. H. M. J., Vanderlocht, J., Schnijderberg, M. C. A., van der Poel, M. W. M., Leewis, B., Hesselink, R., Manz, M. G., Katsura, Y., Kawamoto, H., Germeraad, W. T. V., & Bos, G. M. J. (2010). In vitro-differentiated T/natural killer-cell progenitors derived from human CD34(+) cells mature in the thymus. Blood, 115(2), 261-264. https://doi.org/10.1182/blood-2009-05-223990

@article{fc1df434bdde45ee9dc303524cc3f103,

title = "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-alpha beta(+) 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. ( Blood. 2010; 115:261-264)",

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

year = "2010",

month = jan,

day = "14",

doi = "10.1182/blood-2009-05-223990",

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volume = "115",

pages = "261--264",

journal = "Blood",

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publisher = "The American Society of Hematology",

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Meek, B, Cloosen, S, Borsotti, C, Van Elssen, CHMJ, Vanderlocht, J, Schnijderberg, MCA, van der Poel, MWM, Leewis, B, Hesselink, R, Manz, MG, Katsura, Y, Kawamoto, H, Germeraad, WTV & Bos, GMJ 2010, 'In vitro-differentiated T/natural killer-cell progenitors derived from human CD34(+) cells mature in the thymus', Blood, vol. 115, no. 2, pp. 261-264. https://doi.org/10.1182/blood-2009-05-223990

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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

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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(-/-)gamma(-/-)(c) mice, these cells selectively home to the thymus and differentiate toward surface T-cell receptor-alpha beta(+) 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. ( Blood. 2010; 115:261-264)

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(-/-)gamma(-/-)(c) mice, these cells selectively home to the thymus and differentiate toward surface T-cell receptor-alpha beta(+) 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. ( Blood. 2010; 115:261-264)

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DO - 10.1182/blood-2009-05-223990

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SN - 0006-4971

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