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自杀基因介导的细胞疗法:一种用于可扩展的人类多能干细胞质量控制的新方法。

Suicide gene-enabled cell therapy: A novel approach to scalable human pluripotent stem cell quality control.

作者信息

Gysel Emilie, Larijani Leila, Kallos Michael S, Krawetz Roman J

机构信息

McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada.

Department of Biomedical Engineering, University of Calgary, Calgary, AB, Canada.

出版信息

Bioessays. 2023 Nov;45(11):e2300037. doi: 10.1002/bies.202300037. Epub 2023 Aug 15.

DOI:10.1002/bies.202300037
PMID:37582645
Abstract

There are an increasing number of cell therapy approaches being studied and employed world-wide. An emerging area in this field is the use of human pluripotent stem cell (hPSC) products for the treatment of injuries/diseases that cannot be effectively managed through current approaches. However, as with any cell therapy, vast numbers of functional and safe cells are required. Bioreactors provide an attractive avenue to generate clinically relevant cell numbers with decreased labour and decreased batch to batch variation. Yet, current methods of performing quality control are not readily scalable to the cell densities produced during bioreactor scale-up. One potential solution is the application of inducible/controllable suicide genes that can trigger cell death in unwanted cell types. These types of approaches have been demonstrated to increase the quality and safety of the resultant cell products. In this review, we will provide background on these approaches and how they could be used together with bioreactor technology to create effective bioprocesses for the generation of high quality and safe hPSCs for use in regenerative medicine approaches.

摘要

全球范围内正在研究和应用越来越多的细胞治疗方法。该领域一个新兴的方向是使用人类多能干细胞(hPSC)产品来治疗目前方法无法有效处理的损伤/疾病。然而,与任何细胞治疗一样,需要大量功能正常且安全的细胞。生物反应器提供了一条有吸引力的途径,可在减少人工操作和批次间差异的情况下产生临床相关数量的细胞。然而,目前执行质量控制的方法不容易扩展到生物反应器放大过程中产生的细胞密度。一种潜在的解决方案是应用可诱导/可控的自杀基因,该基因可触发不需要的细胞类型的细胞死亡。这些方法已被证明可提高所得细胞产品的质量和安全性。在本综述中,我们将提供这些方法的背景信息,以及它们如何与生物反应器技术一起用于创建有效的生物工艺,以生成用于再生医学方法的高质量和安全的hPSC。

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