Transient Regenerative Potential of the Neonatal Mouse Heart

By E. Porrello, A. Mahmoud, E. Simpson, Joseph A. Hill, J. Richardson, E. Olson, Hesham A. Sadek. Science, 2011

2,476 citations recorded by the source corpus.

The heart in a newborn mouse can rebuild itself after injury, but this regenerative capacity is lost within a few days. Certain fish and amphibians retain a robust capacity for cardiac regeneration throughout life, but the same is not true of the adult mammalian heart. Whether the capacity for cardiac regeneration is absent in mammals or whether it exists and is switched off early after birth has been unclear. We found that the hearts of 1-day-old neonatal mice can regenerate after partial surgical resection, but this capacity is lost by 7 days of age. This regenerative response in 1-day-old mice was characterized by cardiomyocyte proliferation with minimal hypertrophy or fibrosis, thereby distinguishing it from repair processes. Genetic fate mapping indicated that the majority of cardiomyocytes within the regenerated tissue originated from preexisting cardiomyocytes. Echocardiography performed 2 months after surgery revealed that the regenerated ventricular apex had normal systolic function. Thus, for a brief period after birth, the mammalian heart appears to have the capacity to regenerate.

Subfields: Epidemiology, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/9781bc371213e17dfca6134248d5c4843689167f

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Citations in the corpus

Cardiomyocyte proliferation contributes to heart growth in young humans (2013, background): “In biological models that, unlike adult humans, regenerate myocardium, cardiomyocyte proliferation is important for regeneration as well as postnatal heart growth (10, 11).”
Cardiac fibrosis in myocardial infarction—from repair and remodeling to regeneration (2016, background): “Teleostean fish, newts, and embryonic and neonatal rodents are able fully to regenerate an injured area within the myocardium (Becker et al. 1974; Poss et al. 2002; Porrello et al. 2011).”
Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets (2015, background): “As most cardiomyocytes are unable to divide, cardiac hypertrophy is associated with cardiomyocyte enlargement (Porrello et al. 2011; Soonpaa and Field 1998).”
Distinct macrophage lineages contribute to disparate patterns of cardiac recovery and remodeling in the neonatal and adult heart (2014, result): “Consistent with previous studies reporting age-related reduction in the ability to regenerate myocardium after apical resection or coronary artery ligation (10, 11, 13), postnatal day 1 (P1) mice demonstrated minimal mortality after either one or three DT injections.”
Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family (2012, methodology): “Cardiomyocyte proliferation appears to be the major cellular mechanism driving cardiac regeneration in neonatalmice (8) and adult zebrafish (9, 10).”
The Oxygen Rich Postnatal Environment Induces Cardiomyocyte Cell Cycle Arrest Through DNA Damage Response (2014, positive): “However, this regenerative capacity is lost by postnatal day 7 (Porrello et al., 2011b, 2013), which coincides with cardiomyocyte binucleation and cell-cycle arrest (Soonpaa et al., 1996).”
Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction (2018, neutral): “The mammalian neonatal heart has a remarkable capacity to fully regenerate after injury 7 .”
Production of De Novo Cardiomyocytes: Human Pluripotent Stem Cell Differentiation and Direct Reprogramming (2012, neutral): “This regeneration 16 Cell Stem Cell 10, January 6, 2012 ª2012 Elsevier Inc. occurs through the proliferation and dedifferentiation of cardiomyocytes (Jopling et al., 2010), and similar regeneration has been demonstrated in mice, but only within the first week postpartum (Porrello et al., 2011).”
Pathophysiology of Myocardial Infarction (2015, positive): “Recent studies have suggested that neonatal mice can regenerate the heart following apical resection (291), or coronary ligation (292).”
Mammalian Heart Renewal by Preexisting Cardiomyocytes (2012, neutral): “Such an explanation excludes a role for endogenous progenitors in cardiac repair and would be consistent with data emerging from lower vertebrates 8,26 and the neonatal mouse 27 in which preexisting cardiomyocytes are the cellular source for cardiomyocyte repletion.”
The Hippo signalling pathway and its implications in human health and diseases (2022, background): “202 However, recent evidence suggests that YAP activation can induce cardiac regeneration in adult mice.”
Hippo pathway effector Yap promotes cardiac regeneration (2013, background): “Discussion Although the neonatal mouse heart displays a remarkable ability to regenerate after injury (13, 14), this regenerative potential is lost during the first week of life, such that injury thereafter results in loss of cardiomyocytes, fibrosis, and diminished pump function.”