Reestablishment of lost dopaminergic (DA) neuronal innervation in Parkinson’s disease (PD) by implanting DA neurons in the striatum has shown promise for long-term recovery. One shortcoming of this approach is the poor survival rate of the transplanted cells following implantation (typically 3-20% survive); however, a number of studies suggest that enhancement of viability can be achieved by improving the transplantation procedure and treating the implant with certain growth factors. Here we propose the design of an injectable cell-delivery scaffold based on a nanomaterial platform developed in our laboratory. While the scaffold will partially protect encapsulated cells from mechanical injury and host inflammatory cells, its tunable design will provide optimal biophysical properties and extracellular matrix-derived signals to the DA neurons. To further improve the survival and maturation of transplanted DA neurons, neuroprotective vascular endothelial growth factor (VEGF) will be delivered from the scaffold using a VEGF-binding oligonucleotide sequence (aptamer). The aptamer will prevent acute growth factor-mediated toxicity to the encapsulated cells by inactivating the aptamer-bound VEGF and allow for a controlled VEGF release profile. We expect that this strategy will show significant improvement in functional recovery when implemented in a mouse model of PD
|Effective start/end date||6/1/14 → 5/31/16|
- Northwestern Memorial Hospital (Agmt. Signed 7/2/14)
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