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. .

 描述（由适用提供）：抽象的数百万美国人遭受中风的后果，并且在急性窗口以外没有医疗，长期残疾是毁灭性的。这项指导职业发展奖（K08）的最终目标是发展候选人在中风神经科学，干细胞生物学和生物材料脚手架方面的技能，以便他可以成为独立的研究者，熟练地熟练开发生物工程的系统来更好地了解干细胞疗法和中风恢复。为了实现这一目标，候选人将由中风神经科学，干细胞生物学和生物材料设计的专家召集。再加上这种心态，候选人将在干细胞生物学，干细胞推导和中风生物学机制中以及针对干细胞疗法，血管神经病学和生物材料的高级半手和会议中遵循一种具有正式教学的教育计划。最后，候选人将进行一个与他在生物医学工程领域的非凡背景的研究培训计划密切相符的研究项目，乔治博士开发了一种创新的人类神经祖细胞（HNPCS，一种干细胞）的创新导电聚合物支架。拟议的研究的主要目标是开发这种HNPC输送方法，以改善中风恢复并进一步阐明中风修复机制。乔治博士的初步数据表明，电刺激可以调节被认为对中风恢复很重要的关键蛋白质。该研究计划将涉及通过独特的细胞培养模型以及啮齿动物中风模型阐明电刺激的HNPC的旁分泌效应。此外，初步结果表明，据信据信在中风恢复中不可或缺的蛋白质家族的血小板传播会被电场改变，尤其是血小板传播-3将被专门调节以确定其在电刺激的HNPC-Enhanced-Enhanced-Enhanced-enhanced stroke Recession中的作用。诸如阵列层析成像分析和免疫组织学方法之类的新方法将应用于评估神经结构的变化。主要假设是HNPC的电刺激将增加内源修复机制以增强中风恢复。拟议的研究计划的结果将使人们更好地了解中风恢复的电刺激的HNPC机制，并最终导致中风治疗的更智能设计。