Hydrogel Coated Encapsulation of Cells for Liver Disease Stem Cell Therapy

Liver disease forms a large contribution to the number of annual deaths in the UK. The only current cure for end-stage liver disease is a full transplant and the availability of organs is not sufficient to meet current demands. Even with a successful transplant the patient must still regularly take immunosuppressants for the remainder of their life. A potential alternative solution to this problem is the injection of encapsulated cells as a form of stem cell therapy, with a long-term goal being a completely non-intrusive cure. It is worth noting that while the liver forms the focus of this project, this method is not limited solely to it. This method would have wide applications in regenerative medicine as it could also be relevant to treatment of the lung, joints or the heart.

The main aim of this project is to develop a mathematical model that is able to quantify and predict the effectiveness of using hydrogel coated stem cells in vivo to prevent liver disease. We will first derive a model which aims to describe how a hydrogel coating affects a cells mechanics on both the micro and macro-scales. In particular, we will determine how the cell coating modulates the shear stress experienced by the cell from the surrounding viscous fluid. This can then be expanded to consider how a suspension of encapsulated cells are delivered via the blood stream to the liver and their subsequent engraftment. Throughout this project, and with the help of experimental collaborators detailed below, these models will be calibrated and validated using in vitro and in vivo data which is already available. There is much scope for ensuring this forms a novel project; either by the creation of new models to describe the cell/hydrogel behaviour or by employing numerical methods to create a bespoke simulation of the encapsulated cells and their interaction with the liver, as well as through the application of asymptotic analysis.

The content of this project aligns with several of the core EPSRC research areas. These kinds of problems are inherently non-linear and will be solved using continuum mechanics as a framework, and the numerous applications cause it to also fall naturally under the area of mathematical biology. This DPhil project will be part of a collaboration with researchers in Birmingham and Edinburgh. In Birmingham, Alicia El Haj leads a team carrying out in vitro experiments of encapsulated cells in micro fluid systems and the MRC Centre of Regenerative Medicine in Edinburgh will provide animal models. All of this experimental work is funded through an MRC grant and will provide useful data for model validation.