Here, we present a bioengineering approach to emulate the human bone marrow in vitro. Our developmentally inspired method uses self-organization of human hematopoietic stem and progenitor cells and vascular endothelial cells cultured in a three-dimensional microphysiological system to create vascularized, perfusable tissue constructs that resemble the hematopoietic vascular niche of the human marrow. The microengineered niche is capable of multilineage hematopoiesis and can generate functionally mature human myeloid cells that can intravasate into perfused blood vessels, providing a means to model the mobilization of innate immune cells from the marrow. We demonstrate the application of this system by presenting a specialized model of ionizing radiation-induced bone marrow injury and a multiorgan model of acute innate immune responses to bacterial lung infection. Furthermore, we introduce an advanced platform that enables large-scale integration and automated experimentation of the engineered hematopoietic tissues for preclinical screening of myelotoxicity due to anti-cancer drugs.

中文翻译：

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造血血管生态位的自组织和芯片上的新兴先天免疫


在这里，我们提出了一种在 体外模拟人类骨髓的生物工程方法。我们受发育启发的方法利用在三维微生理系统中培养的人类造血干细胞和祖细胞以及血管内皮细胞的自组织来创造类似于人类骨髓造血血管生态位的血管化、可灌注的组织结构。微工程生态位能够进行多谱系造血，并且可以产生功能成熟的人骨髓细胞，这些细胞可以渗入灌注血管，提供了一种模拟先天免疫细胞从骨髓动员的方法。我们通过提出电离辐射诱导的骨髓损伤的专门模型和对细菌性肺部感染的急性先天免疫反应的多器官模型来证明该系统的应用。此外，我们引入了一个先进的平台，该平台能够对工程造血组织进行大规模整合和自动化实验，用于抗癌药物引起的骨髓毒性的临床前筛选。