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

0845239L。建议智力优点：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，以及一种细胞递送治疗心脏病的方法。该系统将作为基于仿生方法将ES细胞转化为完全分化的细胞类型的模型，该方法非常接近心脏中心血管结构的胚胎发育。这种方法克服了目前ES细胞技术在分化效率方面的局限性，目前ES细胞技术主要集中在通过可溶性信号诱导分化。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化珠和不溶性因子来促进分化的细胞功能。主要研究者（PI）的工程系统旨在提供必要的指导线索，包括细胞微环境在发展过程中。PI建议通过分阶段分化过程来实现总体目标，该过程最初将驱动向统一的中胚层祖细胞分化。随后的步骤将促进向可有助于心脏修复的治疗性细胞群的分化。 更广泛的影响：研究目标的成功将导致细胞培养技术，将作为模板的功能，组织工程结构的产生。其目的是设计一种方案，用于产生一个容易获得的祖细胞群体结合定制的输送系统，以治疗心肌梗死后的患者。这将为及时的临床解决方案提供科学基础，而组织采集中没有任何并发症。教育目标通过工程设计的思想观念紧密联系在一起。作为一名初级教师，PI构思并实施了UT Austin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层次。本提案中所述的外联活动从大学预科一直延伸到大学教师一级。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推广计划使用的教学工具。

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.