Optimizing Stem Cell-Enhanced Stroke Recovery through a Bioengineered Electrically Conductive Polymer Scaffold

通过生物工程导电聚合物支架优化干细胞增强中风恢复

• 批准号: 9147006
• 负责人: Paul George
• 金额: $ 18.8万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9147006
• 关键词: Acute; Affect; Affinity; American; Animal Model; Animals; Architecture; Array tomography; Biocompatible Materials; Biology; Biomedical Engineering; Blood Vessels; Brain; Caregivers; Cell Culture Techniques; Cell Proliferation; Cell Survival; Clinical Trials; Coculture Techniques; Coupled; Data; Derivation procedure; Devices; Disease; Effectiveness; Electric Stimulation; Environment; FDA approved; Family; Gene Expression; Goals; Health; Healthcare; Human; Implant; In Vitro; Infarction; Investigation; K-Series Research Career Programs; Lead; Medical; Mentors; Mentorship; Methods; Modeling; Neurites; Neurology; Neuronal Plasticity; Neurons; Neurosciences; Pathway interactions; Polymers; Protein Family; Proteins; Rattus; Recovery; Recovery of Function; Research; Research Personnel; Research Project Grants; Research Training; Rodent; Role; Stem cells; Stroke; Synapses; Synaptic plasticity; System; Techniques; Technology; Therapeutic; Thrombospondins; Time; Tissue Engineering; Tissues; Transplantation; United States; abstracting; base; cell motility; design; disability; implantation; improved; innovation; interest; knowledge base; neovascularization; nerve stem cell; neurite growth; novel; novel therapeutics; paracrine; polypyrrole; post stroke; pre-clinical; preconditioning; programs; protein expression; relating to nervous system; repaired; research study; response; scaffold; skills; small hairpin RNA; stem cell biology; stem cell therapy; stroke recovery; stroke survivor; stroke therapy; symposium; synaptogenesis; thrombospondin 3

 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. .