Wyrobnik Tom A, Ducci Andrea, Micheletti Martina
Department of Biochemical Engineering, UCL, Gower Street, London WC1E 6BT, UK.
Department of Mechanical Engineering, UCL, Torrington Place, London WC1E 7JE, UK.
Stem Cell Res. 2020 Jul 1;47:101888. doi: 10.1016/j.scr.2020.101888.
Recent advances of stem cell-based therapies in clinical trials have raised the need for large-scale manufacturing platforms that can supply clinically relevant doses to meet an increasing demand. Promising results have been reported using stirred-tank bioreactors, where human Mesenchymal Stromal Cells (hMSCs) were cultured in suspension on microcarriers (MCs), although the formation of microcarrier-cell-aggregates might still limit mass transfer and determine a heterogeneous distribution of hMSCs. A variety of MCs, bioreactor-impeller configurations, and agitation conditions have been established in an attempt to overcome the trade-off of ensuring good suspension while keeping the stresses to a minimum. While understanding and controlling the fluid flow environment of bioreactors has been initially under-appreciated, it has recently gained in popularity in the mission of providing ideal culture environments across different scales. This review article aims to provide a comprehensive overview of how rigorous engineering characterisation studies improved the outcome of biological process development and scale-up efforts. Reconciling these two disciplines is crucial to propose tailored bioprocessing solutions that can provide improved growth environments across a range of scales for the allogeneic cell therapies of the future.
基于干细胞的疗法在临床试验中的最新进展，引发了对大规模制造平台的需求，该平台能够提供临床相关剂量，以满足不断增长的需求。使用搅拌罐生物反应器已报道了一些有前景的结果，其中人间充质基质细胞（hMSCs）在微载体（MCs）上悬浮培养，尽管微载体 - 细胞聚集体的形成可能仍会限制传质，并导致hMSCs分布不均。为了克服在确保良好悬浮的同时将应力降至最低这一权衡问题，已经建立了多种微载体、生物反应器叶轮配置和搅拌条件。虽然最初人们对理解和控制生物反应器的流体流动环境重视不足，但最近它在提供不同规模理想培养环境的任务中越来越受欢迎。这篇综述文章旨在全面概述严格的工程表征研究如何改善生物工艺开发和放大研究的结果。协调这两个学科对于提出定制的生物加工解决方案至关重要，这些解决方案可以为未来的同种异体细胞疗法在一系列规模上提供改善的生长环境。
