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Advances in human mesenchymal stromal cell-based therapies – Towards an integrated biological and engineering approach

Wyrobnik, TA; Ducci, A; Micheletti, M; (2020) Advances in human mesenchymal stromal cell-based therapies – Towards an integrated biological and engineering approach. Stem Cell Research , 47 , Article 101888. 10.1016/j.scr.2020.101888. Green open access

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Abstract

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.

Type: Article
Title: Advances in human mesenchymal stromal cell-based therapies – Towards an integrated biological and engineering approach
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.scr.2020.101888
Publisher version: https://doi.org/10.1016/j.scr.2020.101888
Language: English
Additional information: © 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Keywords: Mesenchymal stromal cell bioprocessing, Impeller design, Stirred-tank bioreactors, Cell therapy process development
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10106460
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