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Dev Biol. 2015 Mar 1;399(1):91-9. doi: 10.1016/j.ydbio.2014.12.018. Epub 2014 Dec 31.

Differential regenerative capacity of neonatal mouse hearts after cryoinjury.

Author information

1
Heart Institute, Los Angeles, California; The Saban Research Institute of Children׳s Hospital Los Angeles, Los Angeles, California.
2
Broad Center of Stem Cell and Regenerative Medicine, University of Southern California, Los Angeles, CA.
3
Heart Institute, Los Angeles, California; The Saban Research Institute of Children׳s Hospital Los Angeles, Los Angeles, California; Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA.
4
The Saban Research Institute of Children׳s Hospital Los Angeles, Los Angeles, California; Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA.
5
Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
6
Heart Institute, Los Angeles, California; The Saban Research Institute of Children׳s Hospital Los Angeles, Los Angeles, California; Department of Surgery, Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA. Electronic address: clien@chla.usc.edu.

Abstract

Neonatal mouse hearts fully regenerate after ventricular resection similar to adult zebrafish. We established cryoinjury models to determine if different types and varying degrees of severity in cardiac injuries trigger different responses in neonatal mouse hearts. In contrast to ventricular resection, neonatal mouse hearts fail to regenerate and show severe impairment of cardiac function post transmural cryoinjury. However, neonatal hearts fully recover after non-transmural cryoinjury. Interestingly, cardiomyocyte proliferation does not significantly increase in neonatal mouse hearts after cryoinjuries. Epicardial activation and new coronary vessel formation occur after cryoinjury. The profibrotic marker PAI-1 is highly expressed after transmural but not non-transmural cryoinjuries, which may contribute to the differential scarring. Our results suggest that regenerative medicine strategies for heart injuries should vary depending on the nature of the injury.

KEYWORDS:

Cardiomyocyte proliferation; Cryoinjury; Epicardium; Neonatal mouse heart regeneration; Neovascularization

PMID:
25555840
PMCID:
PMC4339535
DOI:
10.1016/j.ydbio.2014.12.018
[Indexed for MEDLINE]
Free PMC Article
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