Biological Considerations in Scaling Up Therapeutic Cell Manufacturing

Frontiers in Pharmacology
Darshana S CherianTracy S P Heng

Abstract

Cell therapeutics - using cells as living drugs - have made advances in many areas of medicine. One of the most clinically studied cell-based therapy products is mesenchymal stromal cells (MSCs), which have shown promising results in promoting tissue regeneration and modulating inflammation. However, MSC therapy requires large numbers of cells, the generation of which is not feasible via conventional planar tissue culture methods. Scale-up manufacturing methods (e.g., propagation on microcarriers in stirred-tank bioreactors), however, are not specifically tailored for MSC expansion. These processes may, in principle, alter the cell secretome, a vital component underlying the immunosuppressive properties and clinical effectiveness of MSCs. This review outlines our current understanding of MSC properties and immunomodulatory function, expansion in commercial manufacturing systems, and gaps in our knowledge that need to be addressed for effective up-scaling commercialization of MSC therapy.

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Citations

Oct 1, 2020·International Journal of Molecular Sciences·Sang Eon ParkJong Wook Chang
Feb 2, 2021·Frontiers in Bioengineering and Biotechnology·Marline KirschAntonina Lavrentieva
Feb 23, 2021·Frontiers in Cardiovascular Medicine·Paloma GastelurrutiaCarolina Gálvez-Montón
May 1, 2021·Frontiers in Cell and Developmental Biology·Premkumar JayaramanMohan C Vemuri
Aug 28, 2021·Materials·Vivian Alonso-GoulartLetícia de Souza Castro-Filice
Sep 29, 2021·Journal of Biomedical Materials Research. Part a·Anna Kornmuller, Lauren E Flynn
Aug 3, 2021·Cell Regeneration·Nicole Andréa Corbellini HenckesElizabeth Obino Cirne-Lima

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Methods Mentioned

BETA
bone marrow aspiration

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