Title: Creating the first glucose releasing biomaterials for improving cell therapies
Funder: The Academy of Medical Sciences

Abstract: Neural transplantation is undergoing clinical trials for complex neurodegenerative conditions. Our research group has recently shown that the rapid loss of cells following neural transplantation results specifically from glucose deprivation occurring in the centre of the graft. We propose to alleviate this by developing glucose delivery systems to improve cell transplantation outcomes. Aim 1 – create glucose releasing microspheres which can release glucose to transplanted cells in a sustained manner Aim 2 – prove that these microspheres rescue neurons from ischemic conditions using our recently established models of oxygen-glucose deprivation Glucose is difficult to deliver in a sustained manner because it is a hydrophilic small molecule with no charged regions for electrostatic binding. However, our preliminary experiments have identified a small list of potential monomers/oligomers which can be polymerised with a small enough mesh size to facilitate controlled release of encapsulated glucose. Objective 1 – create a small but diverse library of photocrosslinkable oligomers for glucose encapsulation Objective 2 – use state-of-the-art microfluidic devices to synthesize biodegradable, non-toxic, injectable microspheres capable of releasing glucose for four weeks Objective 3 – use suitable candidate microspheres to rescue neuron progenitor cells in an in vitro model of transplantation ischemia (oxygen-glucose deprivation (OGD)) Outcome – the data gained from this project will be used to apply for funding to show improved graft survival, maturation and function in rodent models of neurodegenerative diseases (in collaboration with Drs Mariah Lelos (BIOSI)/Emma Lane (PHRMY) (Parkinson’s disease) and Prof. Anne Rosser MEDIC/BIOSI (Huntington’s disease)).

Lay abstract: The implantation of new cells into the brain holds the potential to halt, or reverse, the progression of diseases such as Parkinson’s disease and Huntington’s disease. However, when cells are injected into the brain, most of them die very quickly creating a significant problem that needs to be addressed for successful widespread use in the clinic. This death is probably because blood vessels take time to grow into the graft and provide vital nutrients. We have recently shown that it is in fact a lack of glucose that could be the biggest problem facing freshly transplanted cells. We would use this grant funding to make two ground-breaking advances. Firstly, we will develop soft injectable materials (hydrogels – like Jelly) that release glucose in a controlled manner. This would represent the first glucose releasing materials and we have pilot data on how to do this. Secondly, we will show that the released glucose rescues the neurons which will be transplanted into the brains of people with Parkinson’s and Huntington’s disease. This will protect the cells from dying when they are exposed to the harsh conditions they face when transplanted into the brain. Together, this work will create a step-change in how researchers approach cell transplantation strategies and provide a tangible solution to the problem of graft death in the brain. This project is timely, complementing the new round of clinical trials in cell therapies for Parkinson’s disease in the UK (TransEuro), Japan (Kyoto CiRA trial) and USA (Aspen Neuroscience trial).

Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: GENERIC HEALTH RELEVANCE;NEUROLOGICAL