Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffoldsMore about Open Access at the Crick
Authors listSara 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 Ellie Phylactopoulos Constance Maurer Giuseppe Testa Hans J Stauss Sarah A Teichmann Neil J Sebire Adrian Hayday Dominique Bonnet Paola Bonfanti
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.
Journal Nature Communications