Challenges and opportunities in downstream separation processes for mesenchymal stromal cells cultured in microcarrier-based stirred suspension bioreactors,Biotechnology and Bioengineering

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Challenges and opportunities in downstream separation processes for mesenchymal stromal cells cultured in microcarrier-based stirred suspension bioreactors
Biotechnology and Bioengineering ( IF 3.5 ) Pub Date : 2022-08-12 , DOI: 10.1002/bit.28210
Inaara Mawji _{1,

2} , Erin L Roberts _{1,

3} , Tiffany Dang _{1,

3} , Brett Abraham _{1,

3} , Michael S Kallos _{1,

3}

Affiliation

Mesenchymal stromal cells (MSC) are a promising platform for regenerative medicine applications because of their multilineage differentiation abilities and ease of collection, isolation, and growth ex vivo. To meet the demand for clinical applications, large-scale manufacturing will be required using three-dimensional culture platforms in vessels such as stirred suspension bioreactors. As MSCs are an adherent cell type, microcarriers are added to the culture to increase the available surface area for attachment and growth. Although extensive research has been performed on efficiently culturing MSCs using microcarriers, challenges persist in downstream processing, including harvesting, filtration, and volume reduction, which all play a critical role in the translation of cell therapies to the clinic. The objective of this review is to assess the current state of downstream technologies available for microcarrier-based MSC cultures. This includes a review of current research within the three stages: harvesting, filtration, and volume reduction. Using this information, a downstream process for MSCs is proposed, which can be applied to a wide range of applications.

中文翻译：

在基于微载体的搅拌悬浮生物反应器中培养的间充质基质细胞下游分离过程中的挑战和机遇

间充质基质细胞 (MSC) 因其多向分化能力和易于收集、分离和离体生长而成为再生医学应用的一个有前途的平台。为了满足临床应用的需求，将需要在搅拌悬浮生物反应器等容器中使用三维培养平台进行大规模制造。由于 MSC 是一种贴壁细胞类型，因此将微载体添加到培养物中以增加可用于附着和生长的表面积。尽管已经对使用微载体有效培养 MSCs 进行了广泛的研究，但下游处理仍然存在挑战，包括收获、过滤和体积减少，这些都在将细胞疗法转化为临床方面发挥着关键作用。本综述的目的是评估可用于基于微载体的 MSC 培养的下游技术的现状。这包括回顾三个阶段的当前研究：收获、过滤和减容。利用这些信息，提出了 MSCs 的下游工艺，该工艺可应用于广泛的应用。

更新日期：2022-08-12

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