Comment on “Do Neonatal Mouse Hearts Regenerate following Heart Apex Resection”?
2014; Elsevier BV; Volume: 3; Issue: 1 Linguagem: Inglês
10.1016/j.stemcr.2014.06.010
ISSN2213-6711
AutoresMichael I. Kotlikoff, Michael Hesse, Bernd K. Fleischmann,
Tópico(s)Congenital Heart Disease Studies
ResumoMain TextThe recent article by Andersen et al., 2014Andersen D.C. Ganesalingam S. Jensen C.H. Sheikh S.P. Stem Cell Reports. 2014; 2: 406-413Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar reports that following resection of the neonatal heart, "complete regeneration" does not occur, and contrasts these results with those of Porrello et al., 2011Porrello E.R. Mahmoud A.I. Simpson E. Hill J.A. Richardson J.A. Olson E.N. Sadek H.A. Science. 2011; 331: 1078-1080Crossref PubMed Scopus (1605) Google Scholar, who used a similar lesion model. The authors cite our work in support of the fact that complete regeneration does not occur within the neonatal mouse, as we reported that infarction of the neonatal mouse heart is accompanied by inflammatory repair, including CD45+ cell influx, fibrosis, and vascularization of the ablated region of the neonatal myocardium (Jesty et al., 2012Jesty S.A. Steffey M.A. Lee F.K. Breitbach M. Hesse M. Reining S. Lee J.C. Doran R.M. Nikitin A.Y. Fleischmann B.K. Kotlikoff M.I. Proc. Natl. Acad. Sci. USA. 2012; 109: 13380-13385Crossref PubMed Scopus (175) Google Scholar). However, the article misses a crucial point made in that paper, namely, that similar to the report of Porrello et al., neomyogenesis is a critical feature of neonatal heart repair, and one that is unique to the neonatal heart compared to the adult mouse heart (Porrello et al., 2011Porrello E.R. Mahmoud A.I. Simpson E. Hill J.A. Richardson J.A. Olson E.N. Sadek H.A. Science. 2011; 331: 1078-1080Crossref PubMed Scopus (1605) Google Scholar, Jesty et al., 2012Jesty S.A. Steffey M.A. Lee F.K. Breitbach M. Hesse M. Reining S. Lee J.C. Doran R.M. Nikitin A.Y. Fleischmann B.K. Kotlikoff M.I. Proc. Natl. Acad. Sci. USA. 2012; 109: 13380-13385Crossref PubMed Scopus (175) Google Scholar, Hesse et al., 2014Hesse M. Fleischmann B.K. Kotlikoff M.I. Stem Cells. 2014; 32: 1701-1712Crossref PubMed Scopus (35) Google Scholar). Andersen et al.'s findings relative to the inflammation and revascularization that accompanies neonatal heart damage are similar to our results, but we caution that the work provides little quantitative information with respect to the critical issue of the myogenic response. Thus, while their work cites no increase in cell proliferation in the total heart and few proliferating myocytes within the heart apex, we note that these findings are not inconsistent with a model of precursor-driven cell differentiation, as proposed in our study (Jesty et al., 2012Jesty S.A. Steffey M.A. Lee F.K. Breitbach M. Hesse M. Reining S. Lee J.C. Doran R.M. Nikitin A.Y. Fleischmann B.K. Kotlikoff M.I. Proc. Natl. Acad. Sci. USA. 2012; 109: 13380-13385Crossref PubMed Scopus (175) Google Scholar, Hesse et al., 2014Hesse M. Fleischmann B.K. Kotlikoff M.I. Stem Cells. 2014; 32: 1701-1712Crossref PubMed Scopus (35) Google Scholar).We suggest that a focus on the unique capacity of the neonatal heart to undergo neomyogenesis, rather than on the less clearly defined concept of "regeneration," would be valuable. Whether or not "complete regeneration" occurs (and the authors provide compelling data that it does not), the mechanistic basis for neonatal postinjury myogenesis is likely to hold important hints for repair of the adult mammalian heart. Main TextThe recent article by Andersen et al., 2014Andersen D.C. Ganesalingam S. Jensen C.H. Sheikh S.P. Stem Cell Reports. 2014; 2: 406-413Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar reports that following resection of the neonatal heart, "complete regeneration" does not occur, and contrasts these results with those of Porrello et al., 2011Porrello E.R. Mahmoud A.I. Simpson E. Hill J.A. Richardson J.A. Olson E.N. Sadek H.A. Science. 2011; 331: 1078-1080Crossref PubMed Scopus (1605) Google Scholar, who used a similar lesion model. The authors cite our work in support of the fact that complete regeneration does not occur within the neonatal mouse, as we reported that infarction of the neonatal mouse heart is accompanied by inflammatory repair, including CD45+ cell influx, fibrosis, and vascularization of the ablated region of the neonatal myocardium (Jesty et al., 2012Jesty S.A. Steffey M.A. Lee F.K. Breitbach M. Hesse M. Reining S. Lee J.C. Doran R.M. Nikitin A.Y. Fleischmann B.K. Kotlikoff M.I. Proc. Natl. Acad. Sci. USA. 2012; 109: 13380-13385Crossref PubMed Scopus (175) Google Scholar). However, the article misses a crucial point made in that paper, namely, that similar to the report of Porrello et al., neomyogenesis is a critical feature of neonatal heart repair, and one that is unique to the neonatal heart compared to the adult mouse heart (Porrello et al., 2011Porrello E.R. Mahmoud A.I. Simpson E. Hill J.A. Richardson J.A. Olson E.N. Sadek H.A. Science. 2011; 331: 1078-1080Crossref PubMed Scopus (1605) Google Scholar, Jesty et al., 2012Jesty S.A. Steffey M.A. Lee F.K. Breitbach M. Hesse M. Reining S. Lee J.C. Doran R.M. Nikitin A.Y. Fleischmann B.K. Kotlikoff M.I. Proc. Natl. Acad. Sci. USA. 2012; 109: 13380-13385Crossref PubMed Scopus (175) Google Scholar, Hesse et al., 2014Hesse M. Fleischmann B.K. Kotlikoff M.I. Stem Cells. 2014; 32: 1701-1712Crossref PubMed Scopus (35) Google Scholar). Andersen et al.'s findings relative to the inflammation and revascularization that accompanies neonatal heart damage are similar to our results, but we caution that the work provides little quantitative information with respect to the critical issue of the myogenic response. Thus, while their work cites no increase in cell proliferation in the total heart and few proliferating myocytes within the heart apex, we note that these findings are not inconsistent with a model of precursor-driven cell differentiation, as proposed in our study (Jesty et al., 2012Jesty S.A. Steffey M.A. Lee F.K. Breitbach M. Hesse M. Reining S. Lee J.C. Doran R.M. Nikitin A.Y. Fleischmann B.K. Kotlikoff M.I. Proc. Natl. Acad. Sci. USA. 2012; 109: 13380-13385Crossref PubMed Scopus (175) Google Scholar, Hesse et al., 2014Hesse M. Fleischmann B.K. Kotlikoff M.I. Stem Cells. 2014; 32: 1701-1712Crossref PubMed Scopus (35) Google Scholar).We suggest that a focus on the unique capacity of the neonatal heart to undergo neomyogenesis, rather than on the less clearly defined concept of "regeneration," would be valuable. Whether or not "complete regeneration" occurs (and the authors provide compelling data that it does not), the mechanistic basis for neonatal postinjury myogenesis is likely to hold important hints for repair of the adult mammalian heart. The recent article by Andersen et al., 2014Andersen D.C. Ganesalingam S. Jensen C.H. Sheikh S.P. Stem Cell Reports. 2014; 2: 406-413Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar reports that following resection of the neonatal heart, "complete regeneration" does not occur, and contrasts these results with those of Porrello et al., 2011Porrello E.R. Mahmoud A.I. Simpson E. Hill J.A. Richardson J.A. Olson E.N. Sadek H.A. Science. 2011; 331: 1078-1080Crossref PubMed Scopus (1605) Google Scholar, who used a similar lesion model. The authors cite our work in support of the fact that complete regeneration does not occur within the neonatal mouse, as we reported that infarction of the neonatal mouse heart is accompanied by inflammatory repair, including CD45+ cell influx, fibrosis, and vascularization of the ablated region of the neonatal myocardium (Jesty et al., 2012Jesty S.A. Steffey M.A. Lee F.K. Breitbach M. Hesse M. Reining S. Lee J.C. Doran R.M. Nikitin A.Y. Fleischmann B.K. Kotlikoff M.I. Proc. Natl. Acad. Sci. USA. 2012; 109: 13380-13385Crossref PubMed Scopus (175) Google Scholar). However, the article misses a crucial point made in that paper, namely, that similar to the report of Porrello et al., neomyogenesis is a critical feature of neonatal heart repair, and one that is unique to the neonatal heart compared to the adult mouse heart (Porrello et al., 2011Porrello E.R. Mahmoud A.I. Simpson E. Hill J.A. Richardson J.A. Olson E.N. Sadek H.A. Science. 2011; 331: 1078-1080Crossref PubMed Scopus (1605) Google Scholar, Jesty et al., 2012Jesty S.A. Steffey M.A. Lee F.K. Breitbach M. Hesse M. Reining S. Lee J.C. Doran R.M. Nikitin A.Y. Fleischmann B.K. Kotlikoff M.I. Proc. Natl. Acad. Sci. USA. 2012; 109: 13380-13385Crossref PubMed Scopus (175) Google Scholar, Hesse et al., 2014Hesse M. Fleischmann B.K. Kotlikoff M.I. Stem Cells. 2014; 32: 1701-1712Crossref PubMed Scopus (35) Google Scholar). Andersen et al.'s findings relative to the inflammation and revascularization that accompanies neonatal heart damage are similar to our results, but we caution that the work provides little quantitative information with respect to the critical issue of the myogenic response. Thus, while their work cites no increase in cell proliferation in the total heart and few proliferating myocytes within the heart apex, we note that these findings are not inconsistent with a model of precursor-driven cell differentiation, as proposed in our study (Jesty et al., 2012Jesty S.A. Steffey M.A. Lee F.K. Breitbach M. Hesse M. Reining S. Lee J.C. Doran R.M. Nikitin A.Y. Fleischmann B.K. Kotlikoff M.I. Proc. Natl. Acad. Sci. USA. 2012; 109: 13380-13385Crossref PubMed Scopus (175) Google Scholar, Hesse et al., 2014Hesse M. Fleischmann B.K. Kotlikoff M.I. Stem Cells. 2014; 32: 1701-1712Crossref PubMed Scopus (35) Google Scholar). We suggest that a focus on the unique capacity of the neonatal heart to undergo neomyogenesis, rather than on the less clearly defined concept of "regeneration," would be valuable. Whether or not "complete regeneration" occurs (and the authors provide compelling data that it does not), the mechanistic basis for neonatal postinjury myogenesis is likely to hold important hints for repair of the adult mammalian heart. Do Neonatal Mouse Hearts Regenerate following Heart Apex Resection?Andersen et al.Stem Cell ReportsApril 08, 2014In BriefNeonatal mouse hearts have been reported to be regenerative following apex resection. However, in this study, Andersen, Sheikh, and colleagues were unable to reproduce this. Specifically, they found that the resected apex remains lost, cardiomyocyte proliferation is reduced, and that the wounded heart heals by a scarring response similar to that observed in the inert adult heart following damage. Full-Text PDF Open AccessResponse to Sadek et al. and Kotlikoff et al.Andersen et al.Stem Cell ReportsJuly 08, 2014In BriefIn our recent publication in Stem Cell Reports (Andersen et al., 2014), we resected neonatal mouse hearts and examined their ability to regenerate. As described previously (Porrello et al., 2011), we found that all hearts healed but, unexpectedly, this was accompanied with profound scarring of the apex, much like in damaged adult hearts, and little neomyogenesis. In their letter to the editor, Kotlikoff et al., 2014, emphasize the importance of distinguishing between regeneration and neomyogenesis. Full-Text PDF Open Access
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