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

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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.