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

 描述(申请人提供)：数以百万计的美国人遭受中风的后果，在急性窗口之外没有治疗的情况下，长期的残疾是毁灭性的。这项导师职业发展奖(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支架方面的技能，使他可以成为一名独立的研究人员，擅长开发生物工程系统，以更好地了解干细胞疗法和中风康复。为了实现这一目标，候选人将接受中风神经科学、干细胞生物学和生物材料设计方面的专家的指导。除了这种指导，候选人还将继续学习干细胞生物学、干细胞衍生和中风生物学机制方面的正规教学课程，以及专注于干细胞疗法、血管神经学和生物材料的高级研讨会和会议。最后，候选人将开展一个与他的研究培训计划密切相关的研究项目，利用他在生物医学工程方面的特殊背景，George博士为人类神经前体细胞(hNPC，一种干细胞)开发了一种创新的导电聚合物支架。这项研究的主要目标是开发这种hNPC给药方法，以促进卒中恢复并进一步阐明卒中修复机制。乔治博士的初步数据表明，电刺激可以调节被认为对中风康复很重要的关键蛋白质。该研究计划将通过一种独特的细胞培养模型以及在啮齿动物中风模型中阐明电刺激hNPC的旁分泌效应。此外，初步结果表明，血栓反应蛋白家族被认为是卒中恢复过程中不可或缺的一部分，随着电场的变化，尤其是血栓反应蛋白-3将被特异性地调节，以确定其在电刺激hNPC增强的卒中恢复中的作用。新的方法，如阵列断层扫描分析和免疫组织学方法将被应用于评估神经结构的变化。主要的假设是，电刺激hNPC将增加内源性修复机制，以促进中风的恢复。拟议的研究计划的结果将有助于更好地了解电刺激hNPC在卒中康复中的作用机制，并最终导致更智能的卒中疗法设计。。

 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. .