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Immobilised growth factors for scalable cell therapy manufacturing platforms

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posted on 02.01.2018 by Matthew J. Worrallo
Regenerative medicine has the potential to establish or restore normal function in defective tissues and organs. The realisation of such therapies is restricted due to costs, lack of scalability and inefficient manufacturing process controls. A major contributor to cost is the use of expensive growth factors supplemented into media at high concentrations. In vivo, growth factors exist in soluble, immobilised and transmembrane forms, expressed in a spatiotemporal fashion within the stem cell niche. In comparison to soluble equivalents, immobilised growth factors exhibit increased potency, distinct functional activities, improved cell phenotypic control and act in synergy with other soluble and immobilised ligands. To date, most research into immobilised growth factors has been restricted to planar cell culture surfaces such as tissue culture plastics which have limited scalability. To address the scalability limitations, a novel growth factor immobilisation technology was developed using magnetic microparticles which can be scaled with respect to surface area to volume ratio in standard stirred tank bioreactors. Three clinically relevant growth factors, SCF, TPO and GM-CSF were immobilised and were shown to remain functionally active where surface concentration could be manipulated in a number of ways. Through a series of experiments, it was demonstrated that immobilised growth factors exhibited ~10-fold increase in potency compared with soluble equivalents and remain stable for up to 192 hours following recycling during multiple media passages. Immobilised growth factors were able to expand more cells over a longer period of time after transient exposure and finally, the immobilisation technique was successfully applied to the expansion of umbilical cord derived haematopoietic stem cells using immobilised SCF. The immobilisation method described here has the potential to significantly reduce media costs in large scale cell manufacturing processes.

Funding

Loughborough University.

History

School

  • Mechanical, Electrical and Manufacturing Engineering

Publisher

© Matthew James Worrallo

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 2.5 Generic (CC BY-NC-ND 2.5) licence. Full details of this licence are available at: http://creativecommons.org/licenses/by-nc-nd/2.5/

Publication date

2018

Notes

A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University. This thesis has been redacted for reasons relating to the law of copyright. For more information please contact the author.

Language

en

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