Hurdles to uptake of mesenchymal stem cells and their progenitors in therapeutic products

Childs, P. G., Reid, S., Salmeron-Sanchez, M. and Dalby, M. J. (2020) Hurdles to uptake of mesenchymal stem cells and their progenitors in therapeutic products. Biochemical Journal, 477(17), pp. 3349-3366. (doi: 10.1042/BCJ20190382) (PMID:32941644) (PMCID:PMC7505558)

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Twenty-five years have passed since the first clinical trial utilising mesenchymal stomal/stem cells (MSCs) in 1995. In this time academic research has grown our understanding of MSC biochemistry and our ability to manipulate these cells in vitro using chemical, biomaterial, and mechanical methods. Research has been emboldened by the promise that MSCs can treat illness and repair damaged tissues through their capacity for immunomodulation and differentiation. Since 1995, 31 therapeutic products containing MSCs and/or progenitors have reached the market with the level of in vitro manipulation varying significantly. In this review, we summarise existing therapeutic products containing MSCs or mesenchymal progenitor cells and examine the challenges faced when developing new therapeutic products. Successful progression to clinical trial, and ultimately market, requires a thorough understanding of these hurdles at the earliest stages of in vitro pre-clinical development. It is beneficial to understand the health economic benefit for a new product and the reimbursement potential within various healthcare systems. Pre-clinical studies should be selected to demonstrate efficacy and safety for the specific clinical indication in humans, to avoid duplication of effort and minimise animal usage. Early consideration should also be given to manufacturing: how cell manipulation methods will integrate into highly controlled workflows and how they will be scaled up to produce clinically relevant quantities of cells. Finally, we summarise the main regulatory pathways for these clinical products, which can help shape early therapeutic design and testing.

Item Type:Articles
Additional Information:Funding; The authors would like to recognise funding received from EPSRC (EP/P001114/1, EP/S02347X/1), BBSRC (BB/ N018419/1, BB/S018808/1), and the Sir Bobby Charlton Foundation.
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel and Childs, Dr Peter and Dalby, Professor Matthew
Authors: Childs, P. G., Reid, S., Salmeron-Sanchez, M., and Dalby, M. J.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Biochemical Journal
Publisher:Portland Press on behalf of the Biochemical Society
ISSN (Online):1470-8728
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Biochemical Journal 477(17): 3349–3366
Publisher Policy:Reproduced under a Creative Commons Licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173192Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicineManuel Salmeron-SanchezEngineering and Physical Sciences Research Council (EPSRC)EP/P001114/1ENG - Biomedical Engineering
303533EPSRC and SFI Centre for Doctoral Training in Engineered Tissues for Discovery, Industry and MedicineMatthew DalbyEngineering and Physical Sciences Research Council (EPSRC)EP/S02347X/1Institute of Molecular, Cell & Systems Biology
172752Materials exploitation of the biointerface to control MSC quality and niche phenotypeMatthew DalbyBiotechnology and Biological Sciences Research Council (BBSRC)BB/N018419/1Institute of Molecular, Cell & Systems Biology
305758Developing the nanokick bioreactor for commercialisation and cell therapyMatthew DalbyBiotechnology and Biological Sciences Research Council (BBSRC)BB/S018808/1Institute of Molecular, Cell & Systems Biology