Extracellular Matrix Microenvironment for Endothelial and Cardiomyocyte Differentiation

Biological approaches to restore or regenerate healthy cardiovascular tissue using induced pluripotent stem cells (iPSCs) are promising. However, in order to utilize iPSCs therapeutically, the cells must first be efficiently differentiated into the lineage of interest and then delivered to the site of tissue damage. Stem cell phenotype and function are influenced by microenvironmental cues, including the extracellular matric (ECM). The ECM provides structural support and modulates cellular function and phenotype by a variety of signaling mechanism, including those derived from the ECM chemical composition and substrate rigidity. ECMs compositions and matrix rigidity have been shown to enhance differentiation of stem cells but whether these microenvironmental conditions are optimal for endothelial cell (EC) or cardiomyocyte (CM) differentiation is unknown because there has been no systematic study to assess the role of matrix-mediated differentiation. Therefore, the goal of this project is to optimize the ECM microenvironment to promote the differentiation of human iPSCs into ECs and CMs using high-throughput screening of ECM microarrays. The findings from this study will provide a stronger foundation of knowledge and improved methods for the clinical application of iPSC-derived cells for cardiovascular repair.
This inter-hub collaboration brings together the expertise and technology platforms of junior faculty members from three different PCBC Consortium laboratories: Stephane Corbel (Stanford University, Helen Blau Lab), Kathy Ivey (Gladstone Institute, Deepak Srivastava Lab), and Ngan Huang (Stanford University, John Cooke Lab). Through this inter-hub collaboration, we hope to establish a technology platform that can be applicable to other members of the PCBC for regulating the microenvironment to direct differentiation of pluripotent stem cells. Furthermore, this project will further the career development of young faculty members and launch their independent careers in cardiovascular progenitor biology.

Copyright ©2013 NHLBI Progenitor Cell Biology Consortium.

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