CAREER: A novel space-creation concept to enhance the survival and functionality of transplanted human stem cells

CBET-0748129温细胞替代疗法是治疗许多疾病和损伤的最有前途的疗法之一。最近发现了从人类胚胎干细胞和成人干细胞中大量获得多巴胺(DA)神经元所需的体外方案，这使得最终治愈帕金森病(PD)成为可能。然而，干细胞移植的有效性受到体内细胞存活和功能低下的严重影响，这主要是由于与移植过程相关的宿主组织炎症反应导致移植部位形成了富含细胞外基质(ECM)的抑制性瘢痕组织。该项目旨在开发临床适用的细胞替代疗法来治疗神经退行性疾病。在这个项目中，首席研究员(PI)计划通过改善移植的成人干细胞来源的DA神经元的存活率和功能来实现这一目标。该项目基于一个新的空间创造概念，用于PD的细胞替代治疗。该项目的结果将影响包括组织工程、神经科学和发育生物学在内的多个科学和技术领域。研究生、本科生和高中生将通过获得实验技能、技术和学术能力以及准备，为生物医学研究的终身职业生涯进行培训、激励和准备。来自不同背景的学生、妇女和代表性不足的少数群体的积极参与；在课程中展示研究成果；并通过外联活动将研究成果传播到社区，将促进校园多样性并造福社会。

CBET-0748129WenCell replacement therapy represents one of the most promising treatments for many diseases and injuries. Recent discovery of the in vitro protocols necessary to derive dopaminergic (DA) neurons in large quantities from both human embryonic stem cells and adult stem cells has made it possible to ultimately cure Parkinson's disease (PD). However, the efficacy of stem-cell transplantation has been significantly compromised by poor cell survival and functionality in vivo, due primarily to the formation of an inhibitory extracellular matrix (ECM)-rich scar tissue at the transplantation site as a result of host tissue inflammatory response associated with the transplantation procedure. This project is to develop clinically applicable cell replacement therapy for the treatment of neurodegenerative diseases. In this project, the Principal Investigator (PI) plans to achieve this goal by improving the survival and functionality of transplanted human adult stem cell-derived DA neurons in cell replacement therapy for PD based upon a novel space-creation concept.The results of this project will affect multiple scientific and technological communities, including tissue engineering, neuroscience, and developmental biology. Graduate, undergraduate, and high school students will be trained, motivated, and prepared for life-long careers in biomedical research by gaining experimental skills, technical and academic competencies, and readiness. Active involvement of students from diverse backgrounds, women, and underrepresented minority groups; presentation of research results in coursework; and their dissemination into the community through outreach activities will promote campus diversity and benefit society.