A Novel Bioreactor System for Manufacturing in Stem Cell Therapy and Tissue Engineering

The emergence of regenerative medicine offers the potential for new therapies and procedures for diseases and injuries that cannot currently be effectively treated. Regenerative medicine involves the use of living cells and other biological molecules to restore damaged structure and function in human organs and tissues. In addition, the recent excitement arising from the discovery and potential uses of stem cells makes it timely to investigate how stem cell research can be used to treat patients. One of the key issues is how to produce enough living cells (including the very rare stem cells) that have the correct function for these new therapies. The current laboratory cell culture procedures are not efficient, nor are they standardised and cannot meet the current clinical needs. This project aims to address this acute issue by the development of a new method of efficiently culturing stem cells and other human cells to give enough cells required to treat patients. This system will be based on the idea of growing cells using a biomaterial derived from seaweed (alginate) that allows the cells to grow and develop normally. In this work, we will decide what effects the key features of the culture system will have on the growth and function of both human stem cells, and also specific human cell types (eg bone cells). As part of our experiments we will measure how the cells grow and behave in the different culture environments, and compare this to conventional methods.

This proposal addresses one of the key steps in the cell supply chain for regenerative medicine, that is, rapid and efficient expansion of stem cells with predictable and controllable outcomes. The approach we will adopt is to develop a novel bioreactor, based growing the mesenchymal stem cells using chitosan-alginate beads. Media will be fed to the beads such that the cells will have good media transport, thus minimizing mass transfer limitations. The proposed work includes (a) designing and constructing bioreactor encompassing chitosan-alginate beads; (b) demonstrating the bioreactor-based growth of human mesenchymal cells with chitosan-alginate beads; (c) controlled differentiation of mesenchymal populations within the bioreactor; (d) mathematical modelling of cell proliferation and differentiation within the bioreactor system to aid bioprocess design. The proposed bioreactor is an easily scaled system that has the potential to enable the growth and differentation of clinical numbers of cells for therapy.