Direct Cardiac Reprogramming
- 507 Downloads
Recent advances in medical treatment and the development of new mechanical devices have greatly improved the prognosis for heart disease patients. However, heart disease, particularly heart failure, is still a major health issue with continuously increasing numbers of affected patients. Because adult heart muscle has a low regenerative capacity, cardiac function declines with age after cardiac injury. A potential approach to solve this problem is regenerative medicine, aiming at the remuscularization of damaged hearts. Studies conducted in small animals and humans revealed that transplanting various types of cells into failing hearts resulted in the repair of injured hearts and improved cardiac function, but the effects were modest, and further improvement is needed before the method can be widely applied in the clinic. Moreover, true muscle regeneration or cardiac differentiation from so far clinically tested adult stem cells seems to be a rare event, and the beneficial effects of these cell-based therapies are likely due to paracrine factors secreted by the transplanted cells. To regenerate cardiac muscle, it is important to first understand the mechanism of cardiac cell fate determination. Several groups including ours recently found that somatic cells can be directly reprogrammed into cardiomyocyte-like cells using combinations of master regulators. The cardiac reprogramming approach is applicable not only in vitro but also in vivo. It can repair injured hearts and improve cardiac function. Thus, this new technology may open an avenue for regenerative therapy for heart disease.
M.I. was supported by research grants from JST CREST, AMED PRIME, JSPS, Keio University Program for the Advancement of Next Generation Research Projects, Banyu Life Science, Senshin Medical Research Foundation, and Takeda Science Foundation.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants performed by any of the authors.
- Addis RC, Ifkovits JL, Pinto F, Kellam LD, Esteso P, Rentschler S, Christoforou N, Epstein JA, Gearhart JD (2013) Optimization of direct fibroblast reprogramming to cardiomyocytes using calcium activity as a functional measure of success. J Mol Cell Cardiol 60:97–106PubMedPubMedCentralGoogle Scholar
- Fu JD, Stone NR, Liu L, Spencer CI, Qian L, Hayashi Y, Delgado-Olguin P, Ding S, Bruneau BG, Srivastava D (2013) Direct reprogramming of human fibroblasts toward a cardiomyocyte-like state. Stem Cell Rep 1:235–247Google Scholar
- Mathison M, Gersch RP, Nasser A, Lilo S, Korman M, Fourman M, Hackett N, Shroyer K, Yang J, Ma Y et al (2012) In vivo cardiac cellular reprogramming efficacy is enhanced by angiogenic preconditioning of the infarcted myocardium with vascular endothelial growth factor. J Am Heart Assoc 1:e005652PubMedPubMedCentralGoogle Scholar
- Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007b) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872Google Scholar
- Unternaehrer JJ, Zhao R, Kim K, Cesana M, Powers JT, Ratanasirintrawoot S, Onder T, Shibue T, Weinberg RA, Daley GQ (2014) The epithelial-mesenchymal transition factor SNAIL paradoxically enhances reprogramming. Stem Cell Rep 3:691–698Google Scholar
- Yamakawa H, Muraoka N, Miyamoto K, Sadahiro T, Isomi M, Haginiwa S, Kojima H, Umei T, Akiyama M, Kuishi Y et al (2015) Fibroblast growth factors and vascular endothelial growth factor promote cardiac reprogramming under defined conditions. Stem Cell Rep 5:1128–1142Google Scholar