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Updated: Apr 3, 2026
Apical Resection Mouse Model to Study Early Mammalian Heart Regeneration
Published on: January 23, 2016
Sympathetic Reinnervation Is Required for Mammalian Cardiac Regeneration
Ian A White1, Julie Gordon1, Wayne Balkan1
1From the Interdisciplinary Stem Cell Institute (I.A.W., W.B., J.M.H.) Departments of Medicine (W.B., J.M.H.) and Molecular and Cellular Pharmacology (J.M.H.), University of Miami Miller School of Medicine, FL; and Department of Genetics, University of Georgia, Athens (J.G.).
Rationale:
Although mammalian cardiac regeneration can occur in the neonatal period, the factors involved in this process remain to be established. Because tissue and limb regeneration require concurrent reinnervation by the peripheral nervous system, we hypothesized that cardiac regeneration also requires reinnervation.
Objective:
To test the hypothesis that reinnervation is required for innate neonatal cardiac regeneration.
Methods And Results:
We crossed a Wnt1-Cre transgenic mouse with a double-tandem Tomato reporter strain to identify neural crest-derived cell lineages including the peripheral autonomic nerves in the heart. This approach facilitated the precise visualization of subepicardial autonomic nerves in the ventricles using whole mount epifluorescence microscopy. After resection of the left ventricular apex in 2-day-old neonatal mice, sympathetic nerve structures, which envelop the heart under normal conditions, exhibited robust regrowth into the regenerating myocardium. Chemical sympathectomy inhibited sympathetic regrowth and subsequent cardiac regeneration after apical resection significantly (scar size as cross-sectional percentage of viable left ventricular myocardium, n=9; 0.87%±1.4% versus n=6; 14.05±4.4%; P<0.01).
Conclusions:
These findings demonstrate that the profound regenerative capacity of the neonatal mammalian heart requires sympathetic innervation. As such, these data offer significant insights into an underlying basis for inadequate adult regeneration after myocardial infarction, a situation where nerve growth is hindered by age-related influences and scar tissue.
