Expansion of human mesenchymal stem cells in aqueous / aqueous two phase systems

Lead Research Organisation: Loughborough University
Department Name: Chemical Engineering

Abstract

In order that people can live longer and more active lives there is a need to develop new affordable and effective medicines. In some cases cells that we have within our own bodies can be used to repair damaged tissues. However, in adults, this repair mechanism is very limited and often inefficient. Stem cells produced by the body are those that can go on to make all of the different types of cells in the human body and these so called 'stem cells' when harvested have the potential to repair many types of diseased tissue in adults. Although stem cells can now be grown in laboratories, one highly trained person can only grow a few million cells in a week. Since it takes 5 billion heart cells to repair the heart muscle of a heart-attack patient, growing these cells at laboratory scale is useful for research but not for treating multiple patients in practise. This project aims to combine the expertise of both biologists and engineers, to create scalable systems for the "manufacture" of large numbers of stem cells so the potential of stem cell therapies can be realised. Once enough stem cells can be routinely grown and harvested, it is more likely that they can begin to treat a variety of diseases.

Technical Summary

The highly innovative study proposed here will develop a novel isotonic, dispersed aqueous/aqueous two phase system (ATPS) for the reproducible expansion and harvest of multi-potent human mesenchymal stem cells (hMSC) at larger scales in stirred tank bioreactors. The approach to be tested here moves away from the need to use harsh enzymatic treatments to harvest cells from surfaces, relying instead on the controlled disassembly of the 'temporary surface' that the cells are attached to. The successful conclusion of this exciting project will integrate two processes; cell growth and subsequent harvest thereby revolutionising adherent cell culture in stirred bioreactors where a fully functional cell forms the basis of the product necessary for regenerative medicine purposes.

Planned Impact

Quite simply, if sucessful, the impact on adherent cell culture technology would be to revolutionise adherent cell culture where a fully functional cell is the product such as in regenerative medicine bioprocessing. The highly innovative study proposed here will develop a novel isotonic aqueous/aqueous two phase (ATPS) based microcarrier 'particle type' system for the reproducible scalable expansion and harvest of multipotent human mesenchymal stem cells (hMSC). The approach to be tested here moves away from the need to use harsh enzymatic treatments to harvest cells from surfaces relying instead on the controlled removal of the 'temporary surface' from under the cell. Therefore this research will be of benefit for researchers and industrialists in the pharmaceutical sector world-wide so the rights to such IP would carry considerable prestige and be worthy of further exploitation.

Publications

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Description The use of perfluorocarbons to support the growth of human mesenchymal stem cells (hMSCs) as a 'soft' microcarrier was investigated. Human MSCs require a surface to adhere to in order to grow but to meet the potential clinical demand, large numbers of cells need to be generated meaning that the use of traditional 2D culture methods such as T flasks have limitations due to the surface area they present. The use of microcarriers (ie plastic beads) to provide that surface area in a stirred tank environment has already been explored but raises some potential challenges in how to remove the cells from these beads for clinical application. Here the use of perfluorocarbons which can form a surface for the cells to adhere to in the form of a 'soft' microcarrier which can be broken down to release the cells from the surface was studied. The project partners in Birmingham studied the formation of perfluorocarbon droplets (and then microcarriers) in the stirred tank environment and at Loughborough the ability of cells to adhere to and grow on perfluorocarbons was established.
Exploitation Route This new type of microcarrier has the potential to be used by industry to grow mesenchymal stem cells at large scale although further studies would be needed to optimise growth on these.
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology