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通过 3D 生物打印工程改造人类 T 细胞的命运和功能。

Engineering the fate and function of human T-Cells via 3D bioprinting.

机构信息

Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang 110001, People's Republic of China.

Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, People's Republic of China.

出版信息

Biofabrication. 2021 Apr 7;13(3). doi: 10.1088/1758-5090/abd56b.

DOI:10.1088/1758-5090/abd56b
PMID:33348331
Abstract

T-cell immunotherapy holds promise for the treatment of cancer, infection, and autoimmune diseases. Nevertheless, T-cell therapy is limited by low cell expansion efficiencyand functional deficits. Here we describe two 3D bioprinting systems made by different biomaterials that mimic theformation of natural lymph vessels and lymph nodes which modulate T-cell with distinct fates and functions. We observe that coaxial alginate fibers promote T-cell expansion, less exhausted and enable CD4T-cell differentiation into central memory-like phenotype (Tcm), CD8T-cells differentiation into effector memory subsets (Tem), while alginate-gelatin scaffolds bring T-cells into a relatively resting state. Both of the two bioprinting methods are strikingly different from a standard suspension system. The former bioprinting method yields a new system for T-cell therapy and the latter method can be useful for making an immune-chip to elucidate links between immune response and disease.

摘要

T 细胞免疫疗法有望治疗癌症、感染和自身免疫性疾病。然而,T 细胞疗法受到细胞扩增效率低和功能缺陷的限制。在这里,我们描述了两种由不同生物材料制成的 3D 生物打印系统,这些系统模拟了天然淋巴管和淋巴结的形成,从而调节具有不同命运和功能的 T 细胞。我们观察到,同轴海藻酸盐纤维促进 T 细胞扩增,减少衰竭,并使 CD4T 细胞分化为中央记忆样表型(Tcm),CD8T 细胞分化为效应记忆亚群(Tem),而海藻酸盐-明胶支架使 T 细胞进入相对静止状态。这两种生物打印方法都与标准悬浮系统有明显的不同。前者的生物打印方法为 T 细胞疗法提供了一个新系统,后者的方法可用于制造免疫芯片,以阐明免疫反应与疾病之间的联系。

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