We appreciate the interest that Andersen et al. (2014) have
shown in our work on neonatal cardiac regeneration. Their
recent paper relates directly to resection methodology first
presented by Porrello et al. (2011) and describes a failure to
reproduce the observations made in that study regarding
regeneration after resection. We are puzzled by the results
and conclusion because in the hands of the seven different
groups who authored this letter, this methodology has
proved robust and reproducible and has been used in
several ongoing studies across our different laboratories
that are in various stages of completion (Heallen et al.,
[2013], as well as studies by the Lee, Takeuchi, and Nei
groups that are currently under review). Importantly,
several independent groups had similar observations using
various types of neonatal injury (Strungs et al., 2013; Haubner
et al., 2012; Naqvi et al., 2014; Jesty et al., 2012), where
an increase in cardiomyocytes was also observed. Having
carefully examined the study published by Andersen
et al. (2014), it is our overall impression that methodological
differences are likely to account for the difference in
published results. Although it is difficult to draw clear conclusions
about such differences without a detailed analysis
of primary data, our impression is that variations in surgical
technique, amount of resected myocardium, methods of
quantification of resected and regenerated myocardium,
and methods of assessment of myocyte proliferation form
the basis of the differences seen. In particular, we used ventricular
weight and surface area immediately after resection
and 21 days later to assess the degree of injury and regeneration,
while the Andersen group used HW/BW immediately
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 weight
2 days after resection was in excess of 40%. We have not
examined the effect of resection of such a large segment
of the myocardium, but it is plausible that it not compatible
with regeneration. We stand by the reproducibility of
the initial report and we would be happy to assist Andersen
et al. (2014) with various technical aspects of the neonatal
apical resection method.
