Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.
Department of Chemical and Petroleum Engineering, Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.
Biotechnol Bioeng. 2022 Nov;119(11):3062-3078. doi: 10.1002/bit.28210. Epub 2022 Aug 26.
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.
间充质基质细胞（MSC）因其多能分化能力和易于采集、分离以及体外生长的特点，是再生医学应用的有前途的平台。为了满足临床应用的需求，需要使用搅拌悬浮生物反应器等容器中的三维培养平台进行大规模制造。由于 MSC 是贴壁细胞类型，因此在培养中添加微载体以增加用于附着和生长的可用表面积。尽管已经对使用微载体高效培养 MSC 进行了广泛的研究，但在下游处理中仍然存在挑战，包括收获、过滤和体积减少，所有这些都对细胞治疗向临床转化起着至关重要的作用。本综述的目的是评估目前可用于基于微载体的 MSC 培养的下游技术。这包括对收获、过滤和体积减少三个阶段的当前研究的综述。利用这些信息，提出了一种适用于广泛应用的 MSC 下游工艺。
