Creating microcarriers for improving the survival and integration of cells transplanted to the brain.

Background:

For neurodegenerative diseases such as Parkinson’s disease, where a specific cell type is lost, it is possible to consider replacing these cells to restore the lost function. Early clinical trials with fetal cells have proved the concept that cell replacement can provide beneficial outcomes for some patients.

However, grafted cells survive the transplantation procedure very poorly, with typically less than 10% of the cells surviving in the graft. With the advent of vastly improved cell sources (stem cell derived neurons), it is now time to focus on overcoming the bottleneck in the transplantation process: poor graft survival and integration.

There is mounting evidence to suggest that the dissociation of cells prior to transplantation is a major contributor to cell death post-transplantation. This indicates that anoikis (cell death through a lack of adherence to a matrix) is causing cell death.

Our research group is currently developing microcarrier scaffolds to which dopamine progenitor cells (immature dopamine neurons) can adhere and be cultured. The aim of this project is to determine whether culturing dopamine progenitor cells on microcarriers and transplanting cell loaded microcarriers into rodent models of Parkinson’s improves graft survival, integration and function compared to cells transplanted by standard protocols.

Methods:

By working on this interdisciplinary project, the PhD candidate will learn a range of techniques including biomaterial synthesis, microfluidic flow focussing, cell culture including 3D culture, cell health assays, and cell transplantation to the rodent brain including immunohistochemistry and stereology.  

The project with therefore equip the PhD candidate with a wide range of laboratory skills whilst giving them a firm knowledge base in biomaterials science, cell-based therapies, Parkinson’s disease and Huntington’s disease. There is also scope for co-delivery of other pharmaceuticals such as biologics (growth factors) or small molecule drugs to aid maturation of the graft. Such a skill set would provide the candidate with an ideal platform for a career in academia or pharmaceutical companies.

The project will take place at Cardiff University, between the School of Pharmacy and Pharmaceutical Sciences and the School of Biosciences. The supervisory team of this interdisciplinary project comprises Dr. Ben Newland, Dr. Mariah Lelos and Prof. Anne Rosser. 

Enquiries regarding the project: Dr Ben Newland, School of Pharmacy and Pharmaceutical Sciences, Cardiff University.

E-mails: newlandb@cardiff.ac.uk

Please use our online application service at: https://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/pharmacy