为可扩展的细胞疗法优化低温保存策略:全面回顾 iPSC 衍生疗法的启示

IF 2.5 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Michael Dobruskin, Geoffrey Toner, Ronald Kander
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引用次数: 0

摘要

现成的细胞疗法具有治疗帕金森病和心力衰竭等疾病的巨大潜力。然而,这些疗法面临着独特的低温保存挑战,尤其是当采用脑内注射或心外膜注射等新的给药途径时,就要求低温保存介质能够安全地在解冻后直接给药。目前的做法通常需要进行解冻后清洗以去除二甲基亚砜(Me2SO)这种细胞毒性低温保护剂,这使得现成疗法的开发和临床转化变得更加复杂。为了克服这些障碍,亟需探索不含 Me2SO 的低温保存方法。传统的慢速冷冻方案通常会产生次优的解冻后存活率,而优化冷冻曲线则为提高这些方法的性能提供了大有可为的策略。这篇综合综述探讨了各种细胞疗法平台冷冻保存技术的最新进展,并通过对 iPSC 衍生疗法的具体案例研究来说明可扩展性方面的挑战。通过确定冷冻过程中发生的关键热力学和生化现象,本综述旨在确定独立于细胞类型的方法,以提高冷冻保存策略的效率和功效,从而支持现成细胞疗法的广泛采用和临床成功。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Optimizing cryopreservation strategies for scalable cell therapies: A comprehensive review with insights from iPSC‐derived therapies
Off‐the‐shelf cell therapies hold significant curative potential for conditions, such as Parkinson's disease and heart failure. However, these therapies face unique cryopreservation challenges, especially when novel routes of administration, such as intracerebral or epicardial injection, require cryopreservation media that are safe for direct post‐thaw administration. Current practices often involve post‐thaw washing to remove dimethyl sulfoxide (Me2SO), a cytotoxic cryoprotective agent, which complicates the development and clinical translation of off‐the‐shelf therapies. To overcome these obstacles, there is a critical need to explore Me2SO‐free cryopreservation methods. While such methods typically yield suboptimal post‐thaw viability with conventional slow‐freeze protocols, optimizing freezing profiles offers a promising strategy to enhance their performance. This comprehensive review examines the latest advancements in cryopreservation techniques across various cell therapy platforms, with a specific case study of iPSC‐derived therapies used to illustrate the scalability challenges. By identifying key thermodynamic and biochemical phenomena that occur during freezing, this review aims to identify cell‐type independent approaches to improve the efficiency and efficacy of cryopreservation strategies, thereby supporting the widespread adoption and clinical success of off‐the‐shelf cell therapies.
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来源期刊
Biotechnology Progress
Biotechnology Progress 工程技术-生物工程与应用微生物
CiteScore
6.50
自引率
3.40%
发文量
83
审稿时长
4 months
期刊介绍: Biotechnology Progress , an official, bimonthly publication of the American Institute of Chemical Engineers and its technological community, the Society for Biological Engineering, features peer-reviewed research articles, reviews, and descriptions of emerging techniques for the development and design of new processes, products, and devices for the biotechnology, biopharmaceutical and bioprocess industries. Widespread interest includes application of biological and engineering principles in fields such as applied cellular physiology and metabolic engineering, biocatalysis and bioreactor design, bioseparations and downstream processing, cell culture and tissue engineering, biosensors and process control, bioinformatics and systems biology, biomaterials and artificial organs, stem cell biology and genetics, and plant biology and food science. Manuscripts concerning the design of related processes, products, or devices are also encouraged. Four types of manuscripts are printed in the Journal: Research Papers, Topical or Review Papers, Letters to the Editor, and R & D Notes.
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