TY - JOUR
T1 - Ischemic tolerance and cardiac repair in the spiny mouse (Acomys)
AU - Koopmans, Tim
AU - van Beijnum, Henriette
AU - Roovers, Elke F.
AU - Tomasso, Antonio
AU - Malhotra, Divyanshu
AU - Boeter, Jochem
AU - Psathaki, Olympia E.
AU - Versteeg, Danielle
AU - van Rooij, Eva
AU - Bartscherer, Kerstin
N1 - Funding Information:
We thank the Bayer AG and Peter Temple-Smith for providing the Acomys cahirinus founder colony; the Utrecht Sequencing Facility for sequencing, Anko de Graaff and the Hubrecht Imaging Centre for assistance with microscopy, and the Hubrecht animal caretakers for spiny mouse care. We also thank Dennis de Bakker and Sarah Maan Kamel for providing the zebrafish hearts, and members of the Bakkers group for fruitful discussions. We finally wish to thank Catherine Robin for granting us access to the echo device and Joost Sluijter for his insightful comments. This work was supported by the Hubrecht Institute and the European Research Council (ERC-StG-716894) and the German Research Foundation (SFB944—Z-project).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Ischemic heart disease and by extension myocardial infarction is the primary cause of death worldwide, warranting regenerative therapies to restore heart function. Current models of natural heart regeneration are restricted in that they are not of adult mammalian origin, precluding the study of class-specific traits that have emerged throughout evolution, and reducing translatability of research findings to humans. Here, we present the spiny mouse (Acomys spp.), a murid rodent that exhibits bona fide regeneration of the back skin and ear pinna, as a model to study heart repair. By comparing them to ordinary mice (Mus musculus), we show that the acute injury response in spiny mice is similar, but with an associated tolerance to infarction through superior survivability, improved ventricular conduction, and near-absence of pathological remodeling. Critically, spiny mice display increased vascularization, altered scar organization, and a more immature phenotype of cardiomyocytes, with a corresponding improvement in heart function. These findings present new avenues for mammalian heart research by leveraging unique tissue properties of the spiny mouse.
AB - Ischemic heart disease and by extension myocardial infarction is the primary cause of death worldwide, warranting regenerative therapies to restore heart function. Current models of natural heart regeneration are restricted in that they are not of adult mammalian origin, precluding the study of class-specific traits that have emerged throughout evolution, and reducing translatability of research findings to humans. Here, we present the spiny mouse (Acomys spp.), a murid rodent that exhibits bona fide regeneration of the back skin and ear pinna, as a model to study heart repair. By comparing them to ordinary mice (Mus musculus), we show that the acute injury response in spiny mice is similar, but with an associated tolerance to infarction through superior survivability, improved ventricular conduction, and near-absence of pathological remodeling. Critically, spiny mice display increased vascularization, altered scar organization, and a more immature phenotype of cardiomyocytes, with a corresponding improvement in heart function. These findings present new avenues for mammalian heart research by leveraging unique tissue properties of the spiny mouse.
UR - http://www.scopus.com/inward/record.url?scp=85119280838&partnerID=8YFLogxK
U2 - 10.1038/s41536-021-00188-2
DO - 10.1038/s41536-021-00188-2
M3 - Article
AN - SCOPUS:85119280838
SN - 2057-3995
VL - 6
JO - npj Regenerative Medicine
JF - npj Regenerative Medicine
IS - 1
M1 - 78
ER -