Cardiac Regeneration in Model Organisms
- 661 Downloads
Myocardial infarction is the most common cause of cardiac injury in humans and results in acute loss of large numbers of myocardial cells. Unfortunately, the mammalian heart is unable to replenish the cells that are lost following a myocardial infarction and an eventual progression to heart failure can often occur as a result. Regenerative medicine based approaches are actively being developed; however, a complete blueprint on how mammalian hearts can regenerate is still missing. Knowledge gained from studying animal models, such as zebrafish, newt, and neonatal mice, that can naturally regenerate their hearts after injury have provided an understanding of the molecular mechanisms involved in heart repair and regeneration. This research offers novel strategies to overcome the limited regenerative response observed in human patients.
KeywordsCardiac regeneration Model organisms Stem-cell therapy Myocardial infarction Mammalian hearts
This work was done with the support of the California Institute of Regenerative Medicine (TG2-01168), and NIH (NHLBI).
Compliance with Ethics Guidelines
Conflict of Interest
Dr. Laurent Gamba, Dr. Michael Harrison, and Dr. Ching-Ling Lien each declare no potential conflicts of interest relevant to this article.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 1.Forouzanfar MH, Moran AE, Flaxman AD, Roth G, Mensah GA, Ezzati M, et al. Assessing the global burden of ischemic heart disease, part 2: analytic methods and estimates of the global epidemiology of ischemic heart disease in 2010. Glob Heart. 2012;7(4):331–42.PubMedCentralPubMedCrossRefGoogle Scholar
- 14.•Jopling C, Sleep E, Raya M, Martí M, Raya A, Izpisúa Belmonte JC. Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature. 2010;464(7288):606–9. These two papers demonstrate unambiguously that the cardiomyocytes regenerated after injury come from pre-existing cardiomyocytes and not from another cell source.PubMedCentralPubMedCrossRefGoogle Scholar
- 15.•Zhang R, Han P, Yang H, Ouyang K, Lee D, Lin YF, et al. In vivo cardiac reprogramming contributes to zebrafish heart regeneration. Nature. 2013;498(7455):497–501. This paper shows that atrial cardiomyocytes are able to transdifferentiate into ventricular cardiomyocytes and participate in ventricle regeneration in fish embryos and larvae.PubMedCrossRefGoogle Scholar
- 41.•Porrello ER, Mahmoud AI, Simpson E, Hill JA, Richardson JA, Olson EN, et al. Transient regenerative potential of the neonatal mouse heart. Science. 2011;331(6020):1078–80. This paper shows for the first time that neonatal mouse is able to regenerate its heart after injury, showing that mammals have the ability of cardiac regeneration.PubMedCentralPubMedCrossRefGoogle Scholar