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Cardiac Regeneration strategies: Staying young at Heart


The heart tissue of mammals has the limited capacity to regenerate after an injury such as a heart attack or cardiac injuries in part due to the inability to reactivate a cardiac muscle cell and proliferation. Generally injured hearts do not heal themselves. Cardiac muscle cells or cardiomyocytes do not proliferate as much as necessary to replace dead tissue with new, pumping cells. Therefore, most people who had a severe heart attack or other injury related to the heart, will develop heart failure and that’s the leading reason of mortality from Heart Diseases.
As we know that cell proliferation is much essential for the tissue regeneration and cardiomyocytes are highly specialized cells which involves in maintaining the pumping of heart. In previous findings it has been proved that the Hippo pathway stops the Proliferation of cardiomyocytes by inhibiting the activity of YAP pathway. For the reason, a mouse model was developed expressing the adult cardiomyocytes with a version of YAP (YAP5SA) that is impervious to the inhibitory influence of Hippo. By expressing YAP5SA, we could reprogram these specialized adult cardiomyocytes. The reprogrammed cells can also proliferate and new cells can make connections with the existing cardiomyocytes. In this way we can improve Heart Tissue regeneration.




The alternate solution for damaged or lost myocardium describes the derivation of stem cells from cardiomyocytes and their transplantation. Stem cell therapies using adult stem cells and pluripotent stem cells are the new approaches that could potentially achieve the goal of true cardiac regeneration.




Over the past two decades, various stem cell based approaches have been shown to improve left ventricular function in pre-clinical animal model trials. This has been shown to be safe and have advanced our understanding of potential suitable recipients and possible mechanisms of action. However, efficacy in these trials has been inconsistent. Human pluripotent stem cells (hPSCs) are another potential source of stem cells for the cardiac regeneration. They could theoretically provide an unlimited source of cardiomyocytes or progenitor for cardiac tissue. Pre-clinical studies in both small and large animal models have shown robust engraftment and improvements in cardiac function.

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