Supplementary Material for:

Neuregulin stimulation of cardiomyocyte regeneration in mice and human myocardium reveals a therapeutic window

Brian D. Polizzotti, Balakrishnan Ganapathy, Stuart Walsh, Sangita Choudhury, Niyatie Ammanamanchi, David G. Bennett, Cristobal G. dos Remedios, Bernhard J. Haubner, Josef M. Penninger, Bernhard Kühn*

*Corresponding author. E-mail: bernhard.kuhn2{at}chp.edu

Published 1 April 2015, Sci. Transl. Med. 7, 281ra45 (2015)
DOI: 10.1126/scitranslmed.aaa5171

This PDF file includes:

• Materials and Methods
• Results
• Fig. S1. Contribution of cardiomyocyte proliferation to regeneration.
• Fig. S2. Cryoinjured hearts showed loss of sacromeric organization.
• Fig. S3. Characterization of myocardial repair after cryoinjury.
• Fig. S4. Transmural scar persists even after 7 months after cryoinjury.
• Fig. S5. Visualization of scar and quantification of cardiac function by MRI from early administration group.
• Fig. S6. Visualization of scar and quantification of cardiac function by MRI for late administration group.
• Fig. S7. Time course of myocardial repair after cryoinjury from early rNRG1 administration group.
• Fig. S8. Time course of myocardial repair after cryoinjury from late rNRG1 administration group.
• Fig. S9. Failure to visualize transmural scars with late gadolinium enhancement due to low spatial resolution of cMRI in mice.
• Fig. S10. Schematic representation illustrating the nongenetic labeling technique with CFSE.
• Fig. S11. rNRG1-stimulated cardiomyocyte proliferation in infants is age-dependent (2-month-, 6-month-, 1.5- to 5-year-, and 10-year-old patients).
• Reference (46)
• Table S1 (Microsoft Excel format). List of all differentially expressed genes between the BSA and rNRG1 treatment groups relative to sham mice (P < 0.05).
• Table S2. Clinical information of patients with heart disease analyzed for Fig. 6C (H3P activity over age).
• Table S3. Clinical information for normal hearts analyzed for Fig. 6C (H3P activity over age).
• Table S4. Clinical information of patients with heart disease analyzed for Fig. 7D (rNRG1 stimulation).
• Table S5. Clinical information of patients with heart disease analyzed for Fig. 8G (CFSE assay).
• Table S6. Comparison of tissue response after cryoinjury in mice and myocardial disease in human infants (myocardial dysfunction, scar formation, and decreased cardiomyocyte cycling).
• Table S7. Antibody manufacturers and dilutions.
• Table S8. Image acquisition hardware and settings.
• Table S9. Quantification of numeric data.
• Table S10. Human primers for quantitative RT-PCR for calculation of fold change in expression levels.
• Table S11. Mouse primers for quantitative PCR for calculation of fold change in expression levels.

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Other Supplementary Material for this manuscript includes the following:

• Fig.S3.data.pdf
• Fig.S5.data.pdf
• Fig.S6.data.pdf
• Fig.S7.data.pdf
• Fig.S8.data.pdf
• Fig.S11.data.pdf
• Table S1.GeneExpressionData.xlsx
• Movie S1 (.mov format). BSA-treated mouse from early administration.
• Movie S2 (.mov format). rNRG1-treated mouse from early administration.
• Movie S3 (.mov format). BSA-treated mouse from late administration.
• Movie S4 (.mov format). rNRG1-treated mouse from late administration.
• Movie S5 (.mov format). 3D reconstructions show myocardial syncytium adjacent to the scar after early administration (64 dpi).

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