CAREER: Designing Embryonic Stem Cell Culture Systems Based on Developmental Microenvironments in the Heart

0845239 l。智力优势：该项目将产生一个培养系统，从胚胎干细胞（ES）中产生治疗性细胞群，以及一种治疗心脏病的细胞递送方法。该系统将作为胚胎干细胞转化为完全分化细胞类型的模型，该模型基于一种非常接近心脏心血管结构胚胎发育的仿生方法。该方法克服了目前主要通过可溶性信号诱导分化的胚胎干细胞技术在分化效率方面的局限性。这项工作的独特之处在于在3D基质培养中使用蛋白质固定珠和不溶性因子来促进分化的细胞功能。首席研究员（PI）的工程系统被设计为在开发过程中提供必要的指导线索，包括细胞微环境。PI建议通过分阶段分化过程来实现总体目标，该过程将最初推动分化向统一的中胚层祖细胞发展。随后的步骤将促进分化为治疗细胞群，有助于心脏修复。更广泛的影响：研究目标的成功将导致细胞培养技术的发展，该技术将作为产生功能性组织工程结构的模板。目的是设计一种易于获得的祖细胞群的生成方案，并结合量身定制的输送系统来治疗心肌梗死患者。这将为及时的临床解决方案提供科学基础，而不涉及组织收获的并发症。教育目标通过工程设计的思想观念紧密地联系在一起。作为一名初级教师，PI构思并实施了德克萨斯大学奥斯汀分校的整个生物医学工程高级设计序列。PI对设计及其教学有着强烈而持续的热情，并建议设计应融入所有教育水平。本提案中描述的拓展活动从大学预科延伸到大学讲师的水平。将开发具体的工具，包括教学模块，在线课程资源，以及现有的大学预科外展项目使用的教学工具。

0845239L. SuggsIntellectual Merit: This project will result in a culture system to generate a therapeutic cell population from embryonic stem (ES) cells as well as a method for cell delivery to treat cardiac disease. This system will serve as a model for the translation of ES cells to fully differentiated cell types based on a biomimetic approach that closely approximates the embryonic development of cardiovascular structures in the heart. This approach overcomes the limitations in differentiation efficiency of current ES cell technology that is primarily focused on inducing differentiation via soluble signals. The unique aspect of this work is the novel use of protein-immobilized beads and insoluble factors in 3D matrix culture to encourage differentiated cell function. The Principal Investigator's (PI's) engineered systems have been designed to provide the necessary instructional cues that comprise the cellular microenvironment during development. The PI proposes to accomplish the overarching goal through a staged differentiation process that will initially drive differentiation towards a uniform mesodermal progenitor. Subsequent steps will facilitate differentiation towards a therapeutic cell population that can contribute towards cardiac repair. Broader Impact: The success of the research objectives would result in cell culture techniques that will serve as templates for the generation of functional, tissue-engineered constructs. The intent is to design a protocol for the generation of a readily available progenitor cell population combined with a tailored delivery system to treat patients following myocardial infarction. This would provide the scientific foundation for a timely clinical solution with none of the complications involved in tissue harvest. The educational goals are tightly linked via the ideological concept of engineering design. As a junior faculty, the PI has conceived of and implemented the entire Biomedical Engineering senior design sequence at UT Austin. The PI has a strong and continuing passion for design and its instruction and proposes that design should be integrated at all educational levels. The outreach activities described in this proposal extend from precollege through the level of the college instructor. Specific tools will be developed including teaching modules, online course resources, as well as instructional tools for use by existing pre-college outreach programs.