DESCRIPTION (provided by applicant): Abstract Millions of Americans suffer the consequences of stroke, and with no medical treatment outside of the acute window, the long term disability is devastating. The ultimate goal of this Mentored Career Development Award (K08) is to develop the candidate's skills in stroke neuroscience, stem cell biology, and biomaterial scaffolding so that he may become an independent investigator, proficient at developing bioengineered systems to better understand stem cell therapies and stroke recovery. To accomplish this goal, the candidate will be mentored by experts in stroke neuroscience, stem cell biology, and biomaterial design. Coupled with this mentorship, the candidate will pursue an educational program with formal didactics in stem cell biology, stem cell derivation, and mechanisms of stroke biology as well as advanced seminars and conferences focused on stem cell therapeutics, vascular neurology, and biomaterials. Finally, the candidate will undertake a research project closely aligned with his research training plan utilizing his exceptional background in biomedical engineering, Dr. George has developed an innovative conductive polymer scaffold for human neural progenitor cells (hNPCs, a type of stem cell). The primary goal of the proposed research is to develop this hNPC delivery method to improve stroke recovery and further elucidate stroke repair mechanisms. Dr. George's preliminary data suggests that electrical stimulation can modulate key proteins believed to be important in stroke recovery. The research program will involve elucidating the paracrine effects of electrically stimulated hNPCs through a unique cell culture model as well as in a rodent stroke model. Additionally, preliminary results demonstrate that the thrombospondins, a family of protein believed to be integral in stroke recovery, are altered with electrical fields, and in particular thrombospondin-3 will be specifically modulated to determine its role in electrically stimulated hNPC-enhanced stroke recovery. Novel methods such as array tomography analysis and immunohistological methods will be applied to evaluate changes in neural architecture. The primary hypothesis is that electrical stimulation of hNPCs will increase endogenous repair mechanisms to enhance stroke recovery. The results of the proposed research plan will allow for better understanding of the mechanisms of electrically stimulated hNPCs on stroke recovery and ultimately lead to more intelligent design of stroke therapeutics. .

PUBLIC HEALTH RELEVANCE: Stroke is a devastating disease that affects millions of Americans, creating immense burden on stroke survivors and their caregivers. Stem cells offer hope as a potential novel therapy superior to the current time limited treatment options. Our proposed project develops an innovative, stem cell-delivery device aimed at understanding and improving stroke recovery.