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

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 Ce...

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Main Authors: Tom A. Wyrobnik, Andrea Ducci, Martina Micheletti
Format: Article
Language:English
Published: Elsevier 2020-08-01
Series:Stem Cell Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1873506120301896
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author Tom A. Wyrobnik
Andrea Ducci
Martina Micheletti
author_facet Tom A. Wyrobnik
Andrea Ducci
Martina Micheletti
author_sort Tom A. Wyrobnik
collection DOAJ
description 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.
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spelling doaj.art-c72d1c1519bc4c998e8927dca50d5e692022-12-22T01:20:36ZengElsevierStem Cell Research1873-50612020-08-0147101888Advances in human mesenchymal stromal cell-based therapies – Towards an integrated biological and engineering approachTom A. Wyrobnik0Andrea Ducci1Martina Micheletti2Department of Biochemical Engineering, UCL, Gower Street, London WC1E 6BT, UKDepartment of Mechanical Engineering, UCL, Torrington Place, London WC1E 7JE, UKDepartment of Biochemical Engineering, UCL, Gower Street, London WC1E 6BT, UK; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S1873506120301896Mesenchymal stromal cell bioprocessingImpeller designStirred-tank bioreactorsCell therapy process development
spellingShingle Tom A. Wyrobnik
Andrea Ducci
Martina Micheletti
Advances in human mesenchymal stromal cell-based therapies – Towards an integrated biological and engineering approach
Stem Cell Research
Mesenchymal stromal cell bioprocessing
Impeller design
Stirred-tank bioreactors
Cell therapy process development
title Advances in human mesenchymal stromal cell-based therapies – Towards an integrated biological and engineering approach
title_full Advances in human mesenchymal stromal cell-based therapies – Towards an integrated biological and engineering approach
title_fullStr Advances in human mesenchymal stromal cell-based therapies – Towards an integrated biological and engineering approach
title_full_unstemmed Advances in human mesenchymal stromal cell-based therapies – Towards an integrated biological and engineering approach
title_short Advances in human mesenchymal stromal cell-based therapies – Towards an integrated biological and engineering approach
title_sort advances in human mesenchymal stromal cell based therapies towards an integrated biological and engineering approach
topic Mesenchymal stromal cell bioprocessing
Impeller design
Stirred-tank bioreactors
Cell therapy process development
url http://www.sciencedirect.com/science/article/pii/S1873506120301896
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