Development of a Transplantation Platform Technology Applicable for Improving Graft Survival in the Brain

• Applicant: Dr. Ben Newland, Ph.D.
• Subject Area: Biomaterials
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 320041273

Some neurodegenerative diseases, such as Parkinson’s disease, are characterized in part by a loss of a specific subtype of neuron in a specific location. It is therefore possible to consider the replacement of these cells to restore the lost function. With the advent of vastly improved cell sources (such as induced pluripotent stem cell derived neurons), it is now time to focus on overcoming the bottleneck in the transplantation process: poor graft survival. Poor cell survival post transplantation continues to be a major barrier to grafting success with survival rates typically less than 10% for fetal tissue and much lower again for stem cells. This DFG funded project (REF: NE2052/2-1) aims to tackle this problem for an entirely new and previously unexplored angle: biomaterial constructs designed to improve cell survival post transplantation. During this project we have found out that although the literature shows there is a drastic lack of oxygen in the graft core (hypoxia), stem cells can actually survive well in these conditions. We hypothesize that this is due to cells reverting to anaerobic respiration pathways. We have instead shown that glucose is a far more critical factor determining cell survival. To date, there are no glucose releasing biomaterial devices, so this project renewal is requesting funding to synthesize and characterize such materials. These would be based around encapsulation of glucose within a biodegradable poly(β-amino ester) network, using a microfluidic flow focusing device to create uniform microspheres capable of being injected through small gauge needles. Upon recommendation by Dr. Burkhard Jahnen, the original proposal (that requested four years of funding), was shortened to two years with a renewal application possible for the remaining two years. The student working on this project has been extremely hard working and productive (already working on a first author manuscript), and we are now requesting funding to add the important aspect described above to his PhD project.

• DFG Programme: Research Grants
• International Connection: United Kingdom
• Cooperation Partner: Meng Li