Absence of regeneration in the MRL/MpJ mouse heart following infarction or cryoinjury

Abstract

SummaryThe MRL/MpJ mouse has been reported to exhibit minimal scarring and subsequent cardiac regeneration after cryoinjury of the right ventricle. We studied the temporal evolution of infarcts and cryoinjuries in MRL/MpJ and C57BL/6 control mice. Both types of injury in MRL/MpJ mice heal similarly to controls by typical scar formation rather than muscle regeneration, and no differences in cell proliferation, angiogenesis or scar contraction between the two mouse strains were observed.Background-Myocardial infarcts in mammals heal by scar formation rather than formation of new muscle tissue. The MRL/MpJ mouse, however, has been reported to exhibit minimal scarring and subsequent cardiac regeneration after cryoinjury of the right ventricle. Other groups have reported that permanent and temporary ligation of the coronary artery resulted in scarring without regeneration.Methods-To clarify these contradictory results, we studied the temporal evolution of infarcts in MRL/MpJ and C57BL/6 control mice from 1 to 90 days post-injury, and the effects of intrathoracic cryoinjury to 28 days.Results-After infarction, the conversion from necrotic myocardium to granulation tissue and then to scar proceeded identically in the two groups. Infarct DNA synthesis, measured by incorporation of a BrdU pulse, peaked at 4 days in both strains and did not differ between strains at any time point. Endothelial cell and total vascular density in the both the infarcted and non-infarcted cardiac tissue did not differ between groups at any time. Histological analysis of directly cryoinjured right and left ventricular myocardium showed indistinguishable wound healing in both strains, and final scar size was identical in each group.Conclusions-These studies demonstrate that both myocardial infarcts and cryoinjuries in MRL/ MpJ mice heal by typical scar formation rather than muscle regeneration, in a manner very similar to C57BL/6 controls. We conclude that the MRL mouse is not a model for myocardial regeneration.

Development of a human cardiac organoid injury model reveals innate regenerative potential

“…This more closely recapitulates cardiac injury in cases where myocardial infarction causes death to a particular region of the heart. Cryoinjury models have been used extensively in the literature to study cardiac regeneration in lower vertebrates and neonatal rodents, as the technique results in localized cell death with viable surrounding tissue (Chablais and Jazwinska, 2012;Robey and Murry, 2008;Ciulla et al, 2004;Darehzereshki et al, 2015). Cryoinjury was induced in hCOs by application of a small dryice probe that covered the width and one-third of the length of the hCO (∼100 μm×250 μm).…”

Systems approaches to preventing transplanted cell death in cardiac repair

“…This led us to use an ischemia-reperfusion (IR) model of cardiac injury for our long term engraftment studies. This procedure followed established surgical techniques [90,99,100], but myocardial infarction was induced by ligating the left anterior descending coronary artery (LAD) with an 8-0 suture tied around a small piece of silicone tubing placed between the coronary artery and the suture to compress the LAD. After 45 minutes, the suture and tubing were removed to initiate reperfusion.…”

Intramyocardial injection of hydrogel with high interstitial spread does not impact action potential propagation

“…Short axis cross sections (10 μm thick) were taken every 350 μm from apex to base and stained with hematoxylin and eosin (H&E). Cryoinjury size, measured as percent of LV circumferences, was quantified as previously described [38]. Slides were imaged with a Carl Zeiss Observer D.1 and hydrogel spread was quantified using Photoshop software (Adobe Photoshop CS3).…”