Efficient generation of human T cells from a tissue-engineered thymic organoid - PubMed (original) (raw)

R H Evans, R B Foxall, I T Olszak, A H Piascik, K E Hartman, C Brander, T H Meyer, M J Pykett, K T Chabner, S A Kalams, M Rosenzweig, D T Scadden

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

M C Poznansky et al. Nat Biotechnol. 2000 Jul.

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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