Student’s two-tailed t-tests were performed as noted within figure
legends. For comparisons between more than two groups, a one-way
ANOVA with Tukey’s or Dunnett’s post hoc test was performed as noted
within figure legends. P < 0.05 was considered as statistically significant.
Data in Fig. 4i used a Kruskal–Wallis test with Dunn’s multiple compari-
sons test, as these data did not follow a normal distribution. All other
data were found to follow a normal distribution as determined by the
Shapiro–Wilk normality test or Kolmogorov–Smirnov test (α = 0.05). For
experiments involving I–R surgery, the number of mice that received
surgery was determined based on previous experimentation in the
laboratory, which demonstrated a peri-operative surgical mortality
rate of 20%. Only mice that did not survive a given surgical procedure,
or which were found at the time of I–R surgery to have incomplete
reperfusion (failure of slipknot suture release), were excluded from
analysis; otherwise no exclusions occurred. Randomization of mice
within a group to receive a given surgical procedure (I–R versus sham)
or treatment (saline versus cells or zymosan) was not needed because
the mice were genetically identical and were littermates, although
equal sex ratios and age ranges were maintained. Echocardiographic
analysis, quantification of eGFP+ endothelial cells, quantification of
cardiomyocytes in cell cycle, measures of fibrosis, measures of tissue
passive force, in vivo and in vitro gene expression analysis, and analysis
of collagen organization in culture were conducted by investigators
blinded to experimental treatment or procedure. Quantification of
macrophage content by immunohistochemistry was performed using
automated fluorescence threshold analysis in NIS Elements 4.50.
Reporting summary
Further information on research design is available in the Nature
Research Reporting Summary linked to this paper.
Data availability
All raw data generated or analysed in this study are available from the
corresponding author upon reasonable request. Original source data
used to generate graphs in each of the figures and Extended Data figures
are available as Microsoft Excel data sheet files from the correspond-
ing author.
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Acknowledgements This work was supported by grants from the National Institutes of Health
to J.D.M., S.S. and M.N. J.D.M. was supported by the Howard Hughes Medical Institute and the
American Heart Association (19MERIT34370048). R.J.V. was supported by a National Research
Service Award from the NIH (F32 HL128083) and a Career Development Award from the
American Heart Association (19CDA34670044). All flow cytometric data were acquired using
equipment maintained by the Research Flow Cytometry Core in the Division of Rheumatology
at Cincinnati Children’s Hospital Medical Center.Author contributions J.D.M. and R.J.V. conceived the study. R.J.V., M.M., M.A.S., H.K., A.K.J.,
J.A.S., A.J.Y. and V.H. performed experiments and generated all the data shown in the
manuscript. S.S. provided oversight and technical help along with J.A.S. in measuring
myocardial scar mechanical properties. M.N. provided theoretical assessment of the project
and advice in experimental design. J.D.M. and R.J.V interpreted the data and wrote the
manuscript.Competing interests The authors declare no competing interests.Additional information
Supplementary information is available for this paper at https://doi.org/10.1038/s41586-019-
1802-2.
Correspondence and requests for materials should be addressed to J.D.M.
Peer review information Nature thanks Merry Lindsey, Christine Mummery and the other,
anonymous, reviewer(s) for their contribution to the peer review of this work.
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