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首页> 外文期刊>Advanced Functional Materials >Thymus Extracellular Matrix-Derived Scaffolds Support Graft-Resident Thymopoiesis and Long-Term In Vitro Culture of Adult Thymic Epithelial Cells
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Thymus Extracellular Matrix-Derived Scaffolds Support Graft-Resident Thymopoiesis and Long-Term In Vitro Culture of Adult Thymic Epithelial Cells

机译：胸腺细胞外基质衍生的支架支持移植物胸腺孢子和成年胸腺上皮细胞的长期体外培养物

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摘要

The thymus provides the physiological microenvironment critical for the development of T lymphocytes, the cells that orchestrate the adaptive immune system to generate an antigen-specific response. A diverse population of stroma cells provides surface-bound and soluble molecules that orchestrate the intrathymic maturation and selection of developing T cells. Forming an intricate 3D architecture, thymic epithelial cells (TEC) represent the most abundant and important constituent of the thymic stroma. Effective models for in and ex vivo use of adult TEC are still wanting, limiting the engineering of functional thymic organoids and the understanding of the development of a competent immune system. Here a 3D scaffold is developed based on decellularized thymic tissue capable of supporting in vitro and in vivo thymopoiesis by both fetal and adult TEC. For the first time, direct evidences of feasibility for sustained graft-resident T-cell development using adult TEC as input are provided. Moreover, the scaffold supports prolonged in vitro culture of adult TEC, with a retained expression of the master regulator Foxn1. The success of engineering a thymic scaffold that sustains adult TEC function provides unprecedented opportunities to investigate thymus development and physiology and to design and implement novel strategies for thymus replacement therapies.
机译：胸腺为生理学微环境提供了对T淋巴细胞的发展至关重要的，该细胞协调自适应免疫系统以产生抗原特异性反应。不同群体的基质细胞提供方面结合的和可溶性分子，其协调静脉内成熟和选择显影T细胞。形成复杂的3D架构，胸腺上皮细胞（TEC）代表胸腺基质的最丰富和重要的组成。有效的模型和前体内使用成人TEC仍然希望，限制功能性胸腺有机体的工程和对司徒免疫系统的发展的理解。这里，基于胎儿和成年人TEC的体外和体内胸腺过滤器的脱细胞化胸腺组织开发了一种3D支架。首次，提供了使用成人TEC作为输入的持续移植族常驻T细胞开发的可行性直接证据。此外，支架支撑延长成人TEC的体外培养，具有母稳压器FOXN1的保留表达。工程的成功成为维持成人TEC功能的胸腺脚手架，提供了前所未有的机会来调查胸腺发育和生理学以及设计和实施胸腺替代疗法的新策略。

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  • 来源
    《Advanced Functional Materials》 |2021年第20期|2010747.1-2010747.15|共15页
  • 作者

    Asnaghi M. Adelaide; Barthlott Thomas; Gullotta Fabiana; Strusi Valentina; Amovilli Anna; Hafen Katrin; Srivastava Gitika; Oertle Philipp; Toni Roberto; Wendt David; Hollaender Georg A.; Martin Ivan;

  • 作者单位

    Univ Basel Univ Hosp Basel Dept Biomed CH-4031 Basel Switzerland;

    Univ Basel Univ Childrens Hosp Dept Biomed CH-4058 Basel Switzerland;

    Univ Basel Univ Hosp Basel Dept Biomed CH-4031 Basel Switzerland;

    Univ Basel Univ Hosp Basel Dept Biomed CH-4031 Basel Switzerland;

    Univ Basel Univ Hosp Basel Dept Biomed CH-4031 Basel Switzerland;

    Univ Basel Univ Childrens Hosp Dept Biomed CH-4058 Basel Switzerland;

    ARTIDIS AG CH-4057 Basel Switzerland;

    ARTIDIS AG CH-4057 Basel Switzerland|Univ Basel Biozentrum CH-4056 Basel Switzerland|Univ Basel Swiss Nanosci Inst CH-4056 Basel Switzerland;

    Univ Parma Lab Regenerat Morphol & Bioartificial Struct ReMo Dept Med & Surg DIMEC Unit Biomed Biotechnol & Translat Sci SBIBIT I-43121 Parma Italy|Tufts Univ Sch Med Tufts Med Ctr Div Endocrinol Diabet & Metab Boston MA 02111 USA;

    Univ Basel Univ Hosp Basel Dept Biomed CH-4031 Basel Switzerland;

    Univ Basel Univ Childrens Hosp Dept Biomed CH-4058 Basel Switzerland;

    Univ Basel Univ Hosp Basel Dept Biomed CH-4031 Basel Switzerland;

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  • 正文语种 eng
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  • 关键词

    3D scaffolds; decellularization; thymic epithelial cells; thymus engineering;

    机译：3D支架;脱细胞化;胸腺上皮细胞;胸腺工程;

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