Division of Critical Care Medicine, Department of Medicine, Western University, London, Canada.
Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada.
Elife. 2022 Jul 15;11:e75053. doi: 10.7554/eLife.75053.
Mesenchymal stem cells (MSCs) are multipotent cells that demonstrate therapeutic potential for the treatment of acute and chronic inflammatory-mediated conditions. Although controversial, some studies suggest that MSCs may lose their functionality with cryopreservation which could render them non-efficacious. Hence, we conducted a systematic review of comparative pre-clinical models of inflammation to determine if there are differences in in vivo measures of pre-clinical efficacy (primary outcomes) and in vitro potency (secondary outcomes) between freshly cultured and cryopreserved MSCs.
A systematic search on OvidMEDLINE, EMBASE, BIOSIS, and Web of Science (until January 13, 2022) was conducted. The primary outcome included measures of in vivo pre-clinical efficacy; secondary outcomes included measures of in vitro MSC potency. Risk of bias was assessed by the SYRCLE 'Risk of Bias' assessment tool for pre-clinical studies.
Eighteen studies were included. A total of 257 in vivo pre-clinical efficacy experiments represented 101 distinct outcome measures. Of these outcomes, 2.3% (6/257) were significantly different at the 0.05 level or less; 2 favoured freshly cultured and 4 favoured cryopreserved MSCs. A total of 68 in vitro experiments represented 32 different potency measures; 13% (9/68) of the experiments were significantly different at the 0.05 level or less, with seven experiments favouring freshly cultured MSC and two favouring cryopreserved MSCs.
The majority of preclinical primary in vivo efficacy and secondary in vitro potency outcomes were not significantly different (p<0.05) between freshly cultured and cryopreserved MSCs. Our systematic summary of the current evidence base may provide MSC basic and clinical research scientists additional rationale for considering a cryopreserved MSC product in their pre-clinical studies and clinical trials as well as help identify research gaps and guide future related research.
Ontario Institute for Regenerative Medicine.
间充质干细胞（MSCs）是多能细胞，具有治疗急性和慢性炎症介导疾病的治疗潜力。尽管存在争议，但一些研究表明，MSCs 在冷冻保存过程中可能会失去功能，从而使其无效。因此，我们对炎症的临床前模型进行了系统评价，以确定新鲜培养和冷冻保存的 MSCs 之间在体内临床前疗效（主要结局）和体外效力（次要结局）的测量值是否存在差异。
对 OvidMEDLINE、EMBASE、BIOSIS 和 Web of Science 进行了系统检索（截至 2022 年 1 月 13 日）。主要结局包括体内临床前疗效的测量值；次要结局包括 MSC 体外效力的测量值。采用 SYRCLE“临床前研究偏倚风险”评估工具评估偏倚风险。
纳入了 18 项研究。共有 257 项体内临床前疗效实验代表了 101 个不同的结果测量值。其中，2.3%（6/257）在 0.05 水平或更低的水平上有显著差异；2 个结果有利于新鲜培养的 MSC，4 个结果有利于冷冻保存的 MSC。共有 68 项体外实验代表了 32 种不同的效力测量值；13%（9/68）的实验在 0.05 水平或更低的水平上有显著差异，其中 7 个实验有利于新鲜培养的 MSC，2 个实验有利于冷冻保存的 MSC。
新鲜培养和冷冻保存的 MSC 之间，大多数临床前主要的体内疗效和次要的体外效力结果在统计学上没有显著差异（p<0.05）。我们对当前证据基础的系统总结可能为 MSC 基础和临床研究科学家提供更多的理由，考虑在其临床前研究和临床试验中使用冷冻保存的 MSC 产品，并有助于确定研究空白，指导未来的相关研究。
安大略省再生医学研究所。
