Cardiac Regenerative Medicine Without Stem Cell Transplantation

Heart diseases are a leading cause of adult and childhood mortality. The underlying pathology is typically loss of cardiomyocytes progressing towards heart failure, or improper development of cardiomyocytes during embryogenesis leading to congenital heart malformations. Although stem cells may hold promise for cardiac regenerative medicine, a number of obstacles, such as the control of stem cell fate, low-yield commitment, and limited cell survival during differentiation must be overcome before their therapeutic potential can be realized. Moreover, the need for ex vivo cell expansion involves a substantial delay in transplantation after the onset of heart attack. It is now increasingly becoming evident that a novel chemistry, based on the development of multicomponent/multitarget agents, may afford rapid and sustained cardiac repair without stem cell transplantation. The rescuing effect is achieved after direct delivery of these molecules into the heart and results from in vivo epigenetic/transcriptional activation of angiogenic, prosurvival and antifibrotic patterning. Other major fields of investigation are the induction of cell cycle reentry in cardiac-resident cardiomyocytes, or the direct reprogramming of endogenous myocardial fibroblasts into functional cardiomyocytes. To this end, great expectations ensue from the identification of naturally occurring molecules or the development of synthetic compounds avoiding the use of cumbersome and potentially harmful gene delivery by viral vectors to afford efficient somatic cell reprogramming or cardiomyocyte proliferation. Future developments in these fields may pave to way to a cardiac regenerative medicine without stem cell transplantation.