Polacheck William J, Dixon J Brandon, Aw Wen Yih
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill and Raleigh, North Carolina, USA; email:
Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.
Annu Rev Biomed Eng. 2025 May;27(1):73-100. doi: 10.1146/annurev-bioeng-110222-100246. Epub 2025 Jan 22.
The lymphatic vasculature plays critical roles in maintaining fluid homeostasis, transporting lipid, and facilitating immune surveillance. A growing body of work has identified lymphatic dysfunction as contributing to the severity of myriad diseases and to systemic inflammation, as well as modulating drug responses. Here, we review efforts to reconstruct lymphatic vessels in vitro toward establishing humanized, functional models to advance understanding of lymphatic biology and pathophysiology. We first review lymphatic endothelial cell biology and the biophysical lymphatic microenvironment, with a focus on features that are unique to the lymphatics and that have been used as design parameters for lymphatic-on-chip devices. We then discuss the state of the art for recapitulating lymphatic function in vitro, and we acknowledge limitations and challenges to current approaches. Finally, we discuss opportunities and the need for further development of microphysiological lymphatic systems to bridge the gap in model systems between lymphatic cell culture and animal physiology.
淋巴脉管系统在维持体液平衡、运输脂质以及促进免疫监视方面发挥着关键作用。越来越多的研究工作已确定淋巴功能障碍会导致多种疾病的严重程度增加、引发全身炎症以及调节药物反应。在此，我们综述了为在体外重建淋巴管以建立人源化功能性模型所做的努力，以促进对淋巴生物学和病理生理学的理解。我们首先回顾淋巴内皮细胞生物学和生物物理淋巴微环境，重点关注淋巴管特有的特征，这些特征已被用作芯片上淋巴装置的设计参数。然后，我们讨论了体外重现淋巴功能的当前技术水平，并认识到当前方法的局限性和挑战。最后，我们讨论了微生理淋巴系统进一步发展的机遇和需求，以弥合淋巴细胞培养与动物生理学模型系统之间的差距。
