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基于微载体的干细胞生物工艺学:再生医学的 GMP 级培养挑战和未来趋势。

Microcarrier-based stem cell bioprocessing: GMP-grade culture challenges and future trends for regenerative medicine.

机构信息

Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Mexico.

出版信息

Crit Rev Biotechnol. 2021 Nov;41(7):1081-1095. doi: 10.1080/07388551.2021.1898328. Epub 2021 Mar 17.

DOI:10.1080/07388551.2021.1898328
PMID:33730936
Abstract

Recently, stem cell-based therapies have been proposed as an alternative for the treatment of many diseases. Stem cells (SCs) are well known for their capacity to preserve themselves, proliferate, and differentiate into multiple lineages. These characteristics allow stem cells to be a viable option for the treatment of diverse diseases. Traditional methodologies based on 2-dimensional culture techniques (T-flasks and Petri dishes) are simple and well standardized; however, they present disadvantages that limit the production of the cell yield required for regenerative medicine applications. Lately, microcarrier (MC)-based culture techniques have emerged as an attractive platform for expanding stem cells in suspension systems. Although the use of stem cell expansion on MCs has recently shown significant increase, their implementation for medical purposes is been hampered by bottlenecks in upstream and downstream processing. Therefore, there is an urgent need in the development of bioprocesses that simplify stem cell cultures under xeno-free conditions and detachment from MCs without diminishing their pluripotency and viability. A critical analysis of the factors that impact the up and downstream bioprocessing on MC-based stem cell cultures is presented in this review. This analysis aims to raise the awareness of the current drawbacks that limit MC-based stem cell bioprocessing in regenerative medicine and propose alternatives to overcome them.

摘要

最近,基于干细胞的疗法被提议作为治疗许多疾病的替代方法。干细胞(SCs)因其自我维持、增殖和分化为多个谱系的能力而闻名。这些特性使干细胞成为治疗多种疾病的可行选择。基于二维培养技术(T 瓶和培养皿)的传统方法简单且标准化程度高;然而,它们存在一些缺点,限制了再生医学应用所需的细胞产量的生产。最近,基于微载体(MC)的培养技术已成为悬浮系统中扩增干细胞的一种有吸引力的平台。尽管在 MC 上扩增干细胞的使用最近显示出显著增加,但由于上游和下游加工的瓶颈,其在医疗用途中的实施受到阻碍。因此,迫切需要开发在无动物源条件下简化干细胞培养并从 MC 上分离而不降低其多能性和活力的生物工艺。本文对影响基于 MC 的干细胞培养的上下游生物加工的因素进行了批判性分析。该分析旨在提高对当前限制基于 MC 的干细胞生物加工在再生医学中的局限性的认识,并提出克服这些局限性的替代方案。

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