Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, U.S.A.
Department of Biological Engineering, Cornell University, Ithaca, New York 14853, U.S.A.
Biochem Soc Trans. 2021 Apr 30;49(2):693-704. doi: 10.1042/BST20200620.
Leukocytes continuously circulate our body through the blood and lymphatic vessels. To survey invaders or abnormalities and defend our body against them, blood-circulating leukocytes migrate from the blood vessels into the interstitial tissue space (leukocyte extravasation) and exit the interstitial tissue space through draining lymphatic vessels (leukocyte intravasation). In the process of leukocyte trafficking, leukocytes recognize and respond to multiple biophysical and biochemical cues in these vascular microenvironments to determine adequate migration and adhesion pathways. As leukocyte trafficking is an essential part of the immune system and is involved in numerous immune diseases and related immunotherapies, researchers have attempted to identify the key biophysical and biochemical factors that might be responsible for leukocyte migration, adhesion, and trafficking. Although intravital live imaging of in vivo animal models has been remarkably advanced and utilized, bioengineered in vitro models that recapitulate complicated in vivo vascular structure and microenvironments are needed to better understand leukocyte trafficking since these in vitro models better allow for spatiotemporal analyses of leukocyte behaviors, decoupling of interdependent biological factors, better controlling of experimental parameters, reproducible experiments, and quantitative cellular analyses. This review discusses bioengineered in vitro model systems that are developed to study leukocyte interactions with complex microenvironments of blood and lymphatic vessels. This review focuses on the emerging concepts and methods in generating relevant biophysical and biochemical cues. Finally, the review concludes with expert perspectives on the future research directions for investigating leukocyte and vascular biology using the in vitro models.
白细胞通过血液和淋巴管在体内不断循环。为了检测入侵物或异常情况并保护身体免受其侵害，循环中的白细胞从血管迁移到间质组织空间（白细胞渗出），并通过引流的淋巴管重新进入血管（白细胞入胞）。在白细胞迁移的过程中，白细胞识别并响应这些血管微环境中的多种物理和生化线索，以确定适当的迁移和黏附途径。由于白细胞迁移是免疫系统的重要组成部分，并且与许多免疫疾病和相关免疫疗法有关，因此研究人员试图确定可能导致白细胞迁移、黏附和迁移的关键物理和生化因素。尽管体内动物模型的活体成像技术已经取得了显著进展并得到了广泛应用，但仍需要生物工程体外模型来更好地理解白细胞迁移，因为这些体外模型可以更好地进行白细胞行为的时空分析、解耦相互依赖的生物学因素、更好地控制实验参数、进行可重复的实验和定量的细胞分析，以重现复杂的体内血管结构和微环境。本文综述了为研究白细胞与血液和淋巴管复杂微环境的相互作用而开发的生物工程体外模型系统。本文重点介绍了生成相关物理和生化线索的新兴概念和方法。最后，本文总结了使用体外模型研究白细胞和血管生物学的未来研究方向的专家观点。
