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Efficient generation of human T cells from a tissue-engineered thymic organoid

Nature Biotechnology volume 18, pages 729–734 (2000)Cite this article

Abstract

Biocompatible inorganic matrices have been used to enhance bone repair by integrating with endogenous bone architecture. Hypothesizing that a three-dimensional framework might support reconstruction of other tissues as well, we assessed the capacity of a tantalum-coated carbon matrix to support reconstitution of functioning thymic tissue. We engineered a thymic organoid by seeding matrices with murine thymic stroma. Co-culture of human bone marrow-derived hematopoietic progenitor cells within this xenogeneic environment generated mature functional T cells within 14 days. The proportionate T-cell yield from this system was highly reproducible, generating over 70% CD3+ T cells from either AC133+ or CD34+ progenitor cells. Cultured T cells expressed a high level of T-cell receptor excision circles (TREC), demonstrating de novo T lymphopoiesis, and function of fully mature T cells. This system not only facilitates analysis of the T-lymphopoietic potential of progenitor cell populations; it also permits ex vivo genesis of T cells for possible applications in treatment of immunodeficiency.

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Figure 1: Generation of human T cells on the thymic organoid.
Figure 2: (A) Intrasample variability.
Figure 3: (A) T-cell proliferation in response to mitogenic stimulation.

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Author notes

  1. Mark C. Poznansky and Richard H. Evans: The first two authors contributed equally to this work.

Authors and Affiliations

  1. AIDS Research Center and MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, 02129, MA

    Mark C. Poznansky, Richard H. Evans, Russell B. Foxall, Ivona T. Olszak, Anita H. Piascik, Karissa T. Chabner & David T. Scadden

  2. Division of Infectious Diseases, AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, 02129, MA

    Kelly E. Hartman, Christian Brander & Spyros A. Kalams

  3. Cytomatrix, 50 Cummings Park, Woburn, 01801, MA

    Thomas H. Meyer, Mark J. Pykett & Michael Rosenzweig

Authors
  1. Mark C. Poznansky
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Correspondence to David T. Scadden.

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Poznansky, M., Evans, R., Foxall, R. et al. Efficient generation of human T cells from a tissue-engineered thymic organoid. Nat Biotechnol 18, 729–734 (2000). https://doi.org/10.1038/77288

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