Role of Extracellular Matrix in Cardiac Cellular Therapies

The extracellular matrix (ECM) is an essential regulator of homeostasis at the cellular, tissue, and organ level. It is now very well known that ECM dynamic remodeling is indispensable not only for normal growth and development but also recovery from tissue injuries. Indeed, abnormal remodeling of the ECM plays a major role in many pathophysiological processes and contributes to many different pathologies including cardiovascular disorders. Recently, cellular therapies have emerged as a potential therapeutic strategy for restoration of lost cardiomyocytes or their rejuvenation after cardiac damage and injuries. Harnessing the biological properties of ECM could be a viable strategy to enhance the therapeutic effects of cellular therapies by improving the engraftment, integration, survival, and functional adaptation of newly transplanted cells in many different platforms. Conversely, transplanted cells could restore the functionality and original composition of damaged ECM by secreting and depositing new ECM or stimulating normal ECM production by cardiac tissue native cells. Although the ultimate role of cell therapy in treatment of cardiac disorders is still a matter of great debate, the potential utility of ECM in improving the therapeutic effect of transplanted cells and vice versa the potential role of cell therapy as a means to restore the structure and functionality of damaged ECM should be carefully considered in implementation of future clinical cardiovascular cell therapy trials.