Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds

Sara Campinoti, Asllan Gjinovci, Roberta Ragazzini, Luca Zanieri, Linda Ariza-McNaughton, Marco Catucci, Stefan Boeing, Jong Eun Park, John C. Hutchinson, Miguel Muñoz-Ruiz, Pierluigi G. Manti, Gianluca Vozza, Carlo E. Villa, Demetra Ellie Phylactopoulos, Constance Maurer, Giuseppe Testa, Hans J. Stauss, Sarah A. Teichmann, Neil J. Sebire, Adrian C. HaydayDominique Bonnet, Paola Bonfanti

Research output: Contribution to journalArticlepeer-review

Abstract

The thymus is a primary lymphoid organ, essential for T cell maturation and selection. There has been long-standing interest in processes underpinning thymus generation and the potential to manipulate it clinically, because alterations of thymus development or function can result in severe immunodeficiency and autoimmunity. Here, we identify epithelial-mesenchymal hybrid cells, capable of long-term expansion in vitro, and able to reconstitute an anatomic phenocopy of the native thymus, when combined with thymic interstitial cells and a natural decellularised extracellular matrix (ECM) obtained by whole thymus perfusion. This anatomical human thymus reconstruction is functional, as judged by its capacity to support mature T cell development in vivo after transplantation into humanised immunodeficient mice. These findings establish a basis for dissecting the cellular and molecular crosstalk between stroma, ECM and thymocytes, and offer practical prospects for treating congenital and acquired immunological diseases.

Original languageEnglish
Article number6372
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - Dec 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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