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Advances in human mesenchymal stromal cell-based therapies - Towards an integrated biological and engineering approach.
Stem Cell Research ( IF 0.8 ) Pub Date : 2020-07-01 , DOI: 10.1016/j.scr.2020.101888
Tom A Wyrobnik 1 , Andrea Ducci 2 , Martina Micheletti 1
Affiliation  

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.



中文翻译:


基于人类间充质基质细胞的疗法的进展 - 走向综合的生物和工程方法。



基于干细胞的疗法在临床试验中的最新进展提出了对大规模制造平台的需求,这些平台可以提供临床相关剂量,以满足不断增长的需求。使用搅拌罐生物反应器报告了有希望的结果,其中人间充质基质细胞 (hMSC) 在微载体 (MC) 上悬浮培养,尽管微载体-细胞聚集体的形成可能仍然限制传质并决定 hMSC 的异质分布。已经建立了各种MC、生物反应器叶轮配置和搅拌条件,试图克服确保良好悬浮同时将应力保持在最低限度的权衡。虽然理解和控制生物反应器的流体流动环境最初并未得到充分重视,但它最近因提供不同规模的理想培养环境的使命而受到欢迎。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工作的结果。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提供各种规模的改善生长环境。

更新日期:2020-07-01
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