Direct lineage conversion technology is used to convert one cell type to another using transcription factors and micro RNA (different chemical signals) to suppress certain genes and express others. Converting a less vital cell type such as cardiac fibroblasts into cardiac-like myocytes may be a practical solution to replacing damaged cardiomyocytes. Cardiac fibroblasts are the most common type of cell in the heart (2); they are involved in production of connective tissue and maintaining the supporting network surrounding myocytes (3). Cardiac fibroblasts are also involved in fibrosis (scarring) in the heart after cardimyocyte damage. Fibrosis is initially a compensatory mechanism but it can progress adversely causing tissue stiffness and decreased ventricular function (4). Transcription factors that convert cardiac fibroblasts to cardiac-like myocytes have been identified for both human and mouse cells (5). It has been demonstrated that direct delivery of these transcription factors to the site of damage in the heart of a mouse that has experienced myocardial infarction (heart attack) reduces scar formation and blunts deterioration of cardiac function; this is at least in part due to the reprogramming of cardiac fibroblasts to become cardiac-like myocytes (5). It is likely that similar results can be achieved in human hearts. Differences in age, genetics, environmental factors as well as the complexity of the human heart compared to a mouse heart are all factors that still be need be dealt with in order for this treatment to be successful in humans. Overall there appears to be tremendous potential for direct lineage conversion of cardiac fibroblasts to cardiac-like myocytes in human hearts as a method to control cardiomyocyte damage and to replace damaged cardiomyocytes.
1. Masaki, I. et al. (2010) Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes by Defined Factors. Cell. 142(3), 375-386
2. Song, K. et al. (2012) Heart Repair by Reprogramming Non-Myocytes with Cardiac Transcription Factors. Nature. 485, 599-604
3. Snider, P. et al. (2009) Origin of Cardiac Fibroblasts and the Role of Periostin. Circulation Research. 105, 934-947
4. Segura, A. et al. (2014) Fibrosis and Heart Failure. Heart Failure Reviews. 19(2), 173-185
5. Nam, Y. et al. (2013) Reprogramming of Human Fibroblasts Toward a Cardiac Fate. Proceedings of the National Academy of Sciences of the United States of America.110(14), 5588-5593