Abstract 18612: Stem Cell-Derived Extracellular Matrix as a Treatment for Cardiac Remodeling in Post-MI Hearts: A Pilot Study

Abstract

Introduction: Post-myocardial infarction (post-MI) cardiac remodeling and decline in cardiac function remains a vexing problem. Tissue engineered extracellular matrix (ECM) has been used in the past but was restricted by the manufactured structure and mechanical limitations. Here, we use a novel ECM substrate generated by self-assembled cells seeded into spherical molds, that are devoid of the hierarchical structure of ECM fabrication, as a treatment for post-MI cardiac remodeling. Hypothesis: Intramyocardial (IM) injection of ECM particles will result in improved cardiac function and reduced infarct size in post-MI hearts. Methods: Human bone marrow mesenchymal stem cells were cultured and ECM particles were isolated, seeded into micro molds, purified, and characterized. ECM particles were suspended at a concentration of 63,400 particles per mL to create an injectable solution. WT mice underwent left anterior descending (LAD) artery ligation followed by IM injection of 10uL of saline control (n=3) or ECM solution (n=7) to the infarcted area (Figure 1A). Mice then underwent post-operative day 3 (POD 3) and POD 7 echocardiogram to determine changes in cardiac function. Results: There was a trend in improving ejection fraction (EF) in ECM injection group compared to control injection in post-MI at POD 3 while no difference was seen at POD 7 (Figure 1B). No difference in fractional shortening (FS) was observed at POD 3 or POD7 (Figure 1C). Echos at POD 14, POD 21, and POD 28 and additional animals will be added to increase study power. Conclusion: IM injection of ECM trends towards mitigating decline in EF at POD3 and does not affect FS in post-MI hearts. These results are likely underpowered (n=3 versus n=7) and may be a portent of significant myocardial protection post-MI. Our ongoing studies (n=10 per group) investigating the mechanisms by which ECM injections assuage ischemic insult to the myocardium may represent a future strategy for clinical therapy.