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. 2024 Oct 11;135(9):967-969.
doi: 10.1161/CIRCRESAHA.124.325133. Epub 2024 Sep 19.

Noncontractile Stem Cell-Cardiomyocytes Preserve Post-Infarction Heart Function

Elaheh Karbassi  1   2   3 , Dasom Yoo  1   2   3   4 , Amy M Martinson  1   2   3 , Xiulan Yang  1   2   3 , Hans Reinecke  1   2   3 , Michael Regnier  1   2   4   5   6 , Charles E Murry  1   2   3   7   4
Affiliations

Noncontractile Stem Cell-Cardiomyocytes Preserve Post-Infarction Heart Function

Elaheh Karbassi et al. Circ Res. .
No abstract available

Keywords: induced pluripotent stem cells; myocardial infarction; myocardium; myocytes, cardiac; myofibrils.

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Conflict of interest statement

C.E. Murry holds equity in Sana Biotechnology and StemCardia. M. Regnier holds equity in StemCardia. The other authors report no conflicts. Data and materials used in this study are available upon request.

Figures

Figure.
Figure.
Engraftment and functional assessment of noncontractile cardiomyocyte grafts in the infarcted rat heart. A, CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9) editing of TNNI (troponin I) 1 and TNNI3 loci to generate double-knockout (DKO) Wild Type C11 (WTC11) hiPSC line. B, hiPSC cardiac differentiation timeline and cell preparation. Representative flow cytometry plots of cardiac purity using α-actinin labeling. Quantification relative to isotype antibody control. C, Expression of troponin complex proteins in human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) lines by Western blot analysis. Adult rat heart serves as a positive control. D, TNNI DKO hiPSC-CMs form rudimentary myofibrils with poorly formed sarcomeres in vitro. The magnification of the yellow box is shown in the right-hand side figures. Scale bar, 10 µm (inset, 3 µm). E, i, Experimental timeline to assess hiPSC-CM functional efficacy after ischemia/reperfusion (I/R) injury. Vehicle: n=12 animals; wild type (WT): n=14 animals; and TNNI DKO: n=14 animals. ii, Representative immunohistochemistry images of human graft, marked by β-MHC (beta myosin heavy chain; brown), in rat myocardium 3 months post-transplantation. Scale bar, 500 µm. iii, Immunohistochemistry of 3-month human grafts. Scale bar, 10 µm. F, i, Fractional shortening measured by echocardiography, represented for each animal cohort. Error bars represent SEM. Repeated measures 2-way ANOVA, followed by Tukey honestly significant difference (HSD) post hoc testing, was performed to calculate statistical significance for within-group and between-group comparisons at each time point. Within-group comparison across time points (font color denotes group). Between-group comparison at indicated time points: #P=0.037 (vehicle vs WT) and @P=0.039 (vehicle vs TNNI DKO). ii, Change in fractional shortening, relative to baseline, measured by echocardiography at 1 and 3 months post-transplantation. One-way ANOVA, followed by Tukey HSD post hoc testing, was performed to calculate statistical significance for between-group comparisons. APC indicates allophycocyanin; and GAPDH, glyceraldehyde 3-phosphate dehydrogenase.
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References

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