Multi-Investigator Letter on Reproducibility of Neonatal Heart Regeneration following Apical Resection

Abstract

We appreciate the interest that Andersen et al. (2014) haveshowninour workonneonatalcardiacregeneration.Theirrecent paper relates directly to resection methodology firstpresented by Porrello et al. (2011) and describes a failure toreproduce the observations made in that study regardingregeneration after resection. We are puzzled by the resultsandconclusion because inthe hands ofthe seven differentgroups who authored this letter, this methodology hasproved robust and reproducible and has been used inseveral ongoing studies across our different laboratoriesthat are in various stages of completion (Heallen et al.,[2013], as well as studies by the Lee, Takeuchi, and Neigroups that are currently under review). Importantly,several independent groups hadsimilar observations usingvarioustypesofneonatalinjury(Strungsetal.,2013;Haub-ner et al., 2012; Naqvi et al., 2014; Jestyet al., 2012), wherean increase in cardiomyocytes was also observed. Havingcarefully examined the study published by Andersenet al. (2014), it is our overall impression that methodolog-ical differences are likely to account for the difference inpublished results. Although it is difficult to draw clear con-clusions about such differences without a detailed analysisofprimarydata,ourimpressionisthatvariationsinsurgicaltechnique, amount of resected myocardium, methods ofquantification of resected and regenerated myocardium,and methods of assessment of myocyte proliferation formthebasisofthedifferences seen.Inparticular,weusedven-tricularweightandsurfaceareaimmediatelyafterresectionand21days latertoassessthedegree ofinjuryandregener-ation, while the Andersen group used HW/BW immedi-ately after resection and ventricular weight 21 days later.Notably, in Figure 1E of the Andersen et al., 2014, paper,the amount of resected myocardium by ventricular weight2 days after resection was in excess of 40%. We have notexamined the effect of resection of such a large segmentofthemyocardium,butitisplausiblethatitisnotcompat-ible with regeneration. We stand by the reproducibility oftheinitialreportandwewouldbehappytoassistAndersenet al. (2014) with various technical aspects of the neonatalapical resection method.