This grant builds upon the research from a prior grant: Improving the Long-term Survival & Functionality of the Transplanted Human Dopaminergic Neurons Through Space Creation Strategy
Dr. Xuejun Wen was awarded a one-year award in 2004 as part of the MJFF Cell Line II program. Dr. Wen proposed to test a novel biodegradable ‘spacer’ device to improve embryonic stem (ES) cell-derived dopamine neuron graft survival in a PD pre-clinical model. When cells are normally transplanted into a pre-clinical model, it reacts with inflammatory responses causing a ‘scarring’ reaction, which is likely detrimental to the new graft and may explain why graft survival is often poor unless immunosuppression therapy is used. Dr. Wen’s ‘spacer’ device provides a protective well in which transplanted cells can be inserted into the host model. The cells are sheltered from initial host responses, which eventually diminish. The spacer device itself is biodegradable thereby enabling the cells to fully incorporate into the host brain within a few weeks. In addition, if specialized ‘scar suppressive’ cells are first placed in the device and then replaced at a later stage with the transplanted stem cells, graft survival may be even greater.
Dr. Wen has established a collaboration with Dr. Su-Chun Zhang, an expert in working with human ES cells. Dr. Zhang, who is also a Cell Line II awardee, has agreed to provide Dr. Wen with human ES cells that have been converted to dopamine neurons. Dr. Wen will compare transplant survival and behavioral outcome with and without the use of initial scar-suppressing cells and will also compare the outcome to traditional transplant approaches without the spacer device.
Dr Wen demonstrated that hESC-derived dopamine neurons transplanted into the striatum of the 6-OHDA-lesioned pre-clinical model using the methods under study in this project resulted in apparent behavioral improvement and graft survival compared to traditional transplantation method. However, results need further verification.o