Diodati Nickolas G, Qu Ganlin, Mehrad Borna, Schaller Matthew A
Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida College of Medicine, 1200 Newell Drive, Room MSB-M440, Gainesville, FL, 32610, USA.
Respir Res. 2025 May 15;26(1):187. doi: 10.1186/s12931-025-03265-y.
Ex vivo culture techniques have assisted researchers in narrowing the translational gap between the lab and the clinic by allowing the study of biology in human tissues. In pulmonary biology, however, the availability of such tissues is a limiting factor in experimental design and constrains the reproducibility and replicability of these models as scientifically rigorous complements to in vitro or in vivo methods. Cryopreservation of human lung tissue is a strategy to address these limitations by generating cryopreserved biobanks of donors in the ex vivo study of pulmonary biology. Modern cryopreservation solutions, incorporating blends of cryoprotective extracellular macromolecules and cell-permeant non-toxic small molecules, have enabled the long-term storage of human lung tissue, allowing repeated experiments in the same donors and the simultaneous study of the same hypothesis across multiple donors, therefore granting the qualities of reproducibility and replicability to ex vivo systems. Specific considerations are required to properly maintain fundamental aspects of tissue structure, properties, and function throughout the cryopreservation process. The examples of existing cryopreservation systems successfully employed to amass cryobanks, and ex vivo culture techniques compatible with cryopreservation, are discussed herein, with the goal of indicating the potential of cryopreservation in ex vivo human lung tissue culture and highlighting opportunities for cryopreservation to expand the utility of ex vivo human lung culture systems in the pursuit of clinically relevant discoveries.
体外培养技术通过允许在人体组织中进行生物学研究，帮助研究人员缩小了实验室与临床之间的转化差距。然而，在肺生物学领域，此类组织的可获得性是实验设计中的一个限制因素，并制约了这些模型作为体外或体内方法的科学严谨补充的可重复性和可复制性。人肺组织的冷冻保存是一种通过在肺生物学的体外研究中建立供体的冷冻保存生物库来解决这些限制的策略。现代冷冻保存溶液，包含细胞外大分子冷冻保护剂和细胞渗透性无毒小分子的混合物，能够长期保存人肺组织，允许在同一供体上重复进行实验，并在多个供体上同时研究同一假设，从而赋予体外系统可重复性和可复制性的特性。在整个冷冻保存过程中，需要特别考虑以妥善维持组织结构、特性和功能的基本方面。本文讨论了成功用于积累生物库的现有冷冻保存系统的实例，以及与冷冻保存兼容的体外培养技术，目的是指出冷冻保存在体外人肺组织培养中的潜力，并强调冷冻保存扩大体外人肺培养系统在追求临床相关发现中的效用的机会。
