• Open Access

Concise Review: Hematopoietic Stem Cell Transplantation: Targeting the Thymus§

Authors

  • Stéphanie C. De Barros,

    1. Institut de Génétique Moléculaire de Montpellier, UMR5535 CNRS, Université Montpellier 2, Université Montpellier 1, Montpellier, France
    Search for more papers by this author
  • Valérie S. Zimmermann,

    Corresponding author
    1. Institut de Génétique Moléculaire de Montpellier, UMR5535 CNRS, Université Montpellier 2, Université Montpellier 1, Montpellier, France
    • IGMM, 1919 Route de Mende, 34293 Montpellier, Cedex 5, France
    Search for more papers by this author
    • Telephone: 33-4-67-61-36-28; Fax: 33-4-67-04-02-31

  • Naomi Taylor

    Corresponding author
    1. Institut de Génétique Moléculaire de Montpellier, UMR5535 CNRS, Université Montpellier 2, Université Montpellier 1, Montpellier, France
    • IGMM, 1919 Route de Mende, 34293 Montpellier, Cedex 5, France
    Search for more papers by this author
    • Telephone: 33-4-67-61-36-28; Fax: 33-4-67-04-02-31


  • Author contributions: S.C.dB.: conception and design, collection, interpretation and analysis of data, editing and final approval of the manuscript; V.S.Z.; conception and design, financial support, collection, interpretation and analysis of data, editing and final approval of the manuscript; N.T.: conception and design, financial support, collection, interpretation and analysis of data, writing and final approval of the manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    first published online in STEM CELLS EXPRESS April 4, 2013.

Abstract

Allogeneic hematopoietic stem cell (HSC) transplantation can cure patients suffering from diverse genetic and acquired diseases as well as cancers. Nevertheless, under conditions where T-cell reconstitution is critical, the entry of donor progenitors into the thymus remains a major bottleneck. It is assumed that following the intravenous injection of HSC, they first home to the BM. More committed progenitors can then be exported to the thymus in response to a myriad of signals regulating thymus seeding. Notably although, the thymus is not continually receptive to the import of hematopoietic progenitors. Furthermore, as stem cells with self-renewing capacity do not take up residence in the thymus under physiological conditions, the periodic colonization of the thymus is essential for the sustained differentiation of T lymphocytes. As such, we and others have invested significant efforts into exploring avenues that might foster a long-term thymus-autonomous differentiation. Here, we review strategic approaches that have resulted in long-term T-cell differentiation in immunodeficient (SCID) mice, even across histocompatibility barriers. These include the forced thymic entry of BM precursors by their direct intrathymic injection as well as the transplantation of neonatal thymi. The capacity of the thymus to support hematopoietic progenitors with renewal potential will hopefully promote the development of new therapeutic strategies aimed at enhancing T-cell differentiation in patients undergoing HSC transplantation. STEM Cells2013;31:1245–1251

Ancillary