Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds.
Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds.
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DOI：
10.1038/s41467-020-20082-7
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发表时间：
2020-12-11
影响因子：
16.6
通讯作者：
Bonfanti P
中科院分区：
文献类型：
--
作者：
Campinoti S;Gjinovci A;Ragazzini R;Zanieri L;Ariza-McNaughton L;Catucci M;Boeing S;Park JE;Hutchinson JC;Muñoz-Ruiz M;Manti PG;Vozza G;Villa CE;Phylactopoulos DE;Maurer C;Testa G;Stauss HJ;Teichmann SA;Sebire NJ;Hayday AC;Bonnet D;Bonfanti P
胸腺是主要的淋巴器官，对于 T 细胞的成熟和选择至关重要。长期以来，人们对胸腺生成的过程及其临床操纵的潜力一直感兴趣，因为胸腺发育或功能的改变可能导致严重的免疫缺陷和自身免疫。在这里，我们鉴定了上皮-间质杂交细胞，它们能够在体外长期扩增，并且当与胸腺间质细胞和通过全胸腺灌注获得的天然脱细胞细胞外基质（ECM）结合时，能够重建天然胸腺的解剖表型。这种解剖学人类胸腺重建是有功能的，从其移植到人源化免疫缺陷小鼠体内后支持体内成熟 T 细胞发育的能力来判断。这些发现为剖析基质、ECM 和胸腺细胞之间的细胞和分子串扰奠定了基础，并为治疗先天性和获得性免疫疾病提供了实际前景。胸腺对于 T 细胞的成熟和选择至关重要，胸腺缺陷会导致严重的免疫问题。在这里，作者鉴定了一种可在体外扩增的胸腺细胞群，并且可以重新填充天然胸腺基质以生成支持体外和体内成熟 T 细胞发育的组织。
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. The thymus is essential for T cell maturation and selection, and thymic defects result in severe immune problems. Here the authors identify a thymus cell population that is expandable in vitro, and can repopulate natural thymic matrix to generate tissue that supports mature T cell development in vitro and in vivo.
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影响因子：
30.5
作者：
Brennecke P;Reyes A;Pinto S;Rattay K;Nguyen M;Küchler R;Huber W;Kyewski B;Steinmetz LM
通讯作者：
Steinmetz LM
DOI：
10.1084/jem.20131540
发表时间：
2014-02-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Coffey F;Lee SY;Buus TB;Lauritsen JP;Wong GW;Joachims ML;Thompson LF;Zúñiga-Pflücker JC;Kappes DJ;Wiest DL
通讯作者：
Wiest DL
影响因子：
32.4
作者：
Chalmin, Fanny;Mignot, Gregoire;Ghiringhelli, Francois
通讯作者：
Ghiringhelli, Francois
影响因子：
4.4
作者：
Alves, Nuno L.;Huntington, Nicholas D.;Di Santo, James P.
通讯作者：
Di Santo, James P.
影响因子：
32.4
作者：
Colgan, J;Asmal, M;Luban, J
通讯作者：
Luban, J