Impact of Cryopreservation and Freeze-Thawing on Therapeutic Properties of Mesenchymal Stromal/Stem Cells and Other Common Cellular Therapeutics.

IF 2.3 Q4 CELL & TISSUE ENGINEERING
Chasen Cottle, Amanda Paige Porter, Ariel Lipat, Caitlin Turner-Lyles, Jimmy Nguyen, Guido Moll, Raghavan Chinnadurai
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引用次数: 41

Abstract

Purpose of review: Cryopreservation and its associated freezing and thawing procedures-short "freeze-thawing"-are among the final steps in economically viable manufacturing and clinical application of diverse cellular therapeutics. Translation from preclinical proof-of-concept studies to larger clinical trials has indicated that these processes may potentially present an Achilles heel to optimal cell product safety and particularly efficacy in clinical trials and routine use.

Recent findings: We review the current state of the literature on how cryopreservation of cellular therapies has evolved and how the application of this technique to different cell types is interlinked with their ability to engraft and function upon transfer in vivo, in particular for hematopoietic stem and progenitor cells (HSPCs), their progeny, and therapeutic cell products derived thereof. We also discuss pros and cons how this may differ for non-hematopoietic mesenchymal stromal/stem cell (MSC) therapeutics. We present different avenues that may be crucial for cell therapy optimization, both, for hematopoietic (e.g., effector, regulatory, and chimeric antigen receptor (CAR)-modified T and NK cell based products) and for non-hematopoietic products, such as MSCs and induced pluripotent stem cells (iPSCs), to achieve optimal viability, recovery, effective cell dose, and functionality of the cryorecovered cells.

Summary: Targeted research into optimizing the cryopreservation and freeze-thawing routines and the adjunct manufacturing process design may provide crucial advantages to increase both the safety and efficacy of cellular therapeutics in clinical use and to enable effective market deployment strategies to become economically viable and sustainable medicines.

冷冻保存和冻融对间充质基质/干细胞治疗特性的影响及其他常见细胞疗法。
综述目的:冷冻保存及其相关的冷冻和解冻程序(简称“冷冻解冻”)是多种细胞疗法在经济上可行的制造和临床应用的最后步骤之一。从临床前概念验证研究到更大规模的临床试验的转化表明,这些过程可能会成为最佳细胞产品安全性的致命弱点,特别是在临床试验和常规使用中。最近的发现:我们回顾了目前关于细胞低温保存疗法的发展现状,以及这种技术在不同细胞类型中的应用如何与它们在体内移植的能力和功能相关联,特别是造血干细胞和祖细胞(HSPCs)、它们的后代和由此衍生的治疗性细胞产品。我们还讨论了非造血间充质基质/干细胞(MSC)治疗方法的利弊。我们提出了可能对细胞治疗优化至关重要的不同途径,无论是对于造血(例如,效应、调节性和嵌合抗原受体(CAR)修饰的T和NK细胞产品)还是对于非造血产品,如MSCs和诱导多能干细胞(iPSCs),都可以实现最佳的活力、恢复、有效细胞剂量和冷冻恢复细胞的功能。摘要:有针对性地研究优化冷冻保存和冻融程序以及辅助制造工艺设计可能为提高细胞治疗药物在临床应用中的安全性和有效性提供关键优势,并使有效的市场部署策略成为经济上可行和可持续的药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current Stem Cell Reports
Current Stem Cell Reports Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.30
自引率
0.00%
发文量
19
期刊介绍: The goal of this journal is to publish cutting-edge reviews on subjects pertinent to all aspects of stem cell research, therapy, ethics, commercialization, and policy. We aim to provide incisive, insightful, and balanced contributions from leading experts in each relevant domain that will be of immediate interest to a wide readership of clinicians, basic scientists, and translational investigators. We accomplish this aim by appointing major authorities to serve as Section Editors in key subject areas across the discipline. Section Editors select topics to be reviewed by leading experts who emphasize recent developments and highlight important papers published over the past year on their topics, in a crisp and readable format. We also provide commentaries from well-known figures in the field, and an Editorial Board of internationally diverse members suggests topics of special interest to their country/region and ensures that topics are current and include emerging research.
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