Lab-grown, 3D Extracellular Matrix Particles Improve Cardiac Function and Morphology in Myocardial Ischemia.
Publication/Presentation Date
12-20-2024
Abstract
The promise of injection of extracellular matrix (ECM) from animal hearts as a treatment of myocardial ischemia has been limited by immune reactions and harsh ECM-damaging extraction procedures. We developed a novel method to produce lab-grown human 3D acellular ECM particles from human mesenchymal stem cells (MSCs) to mitigate product variability, immunogenicity, and preserve ECM architecture. We hypothesized that intramyocardial injection (I/M) of this novel ECM (dia ~200 microns) would improve cardiac function in a post-myocardial infarction (MI) murine model. WT mice aged 8-10 weeks underwent ligation of the LAD artery and I/M injection of 10 uL ECM or normal saline (n=10/group). Compared to control, ECM-treated hearts showed significant reduction in infarct size (p=0.04), increased capillary density in ischemic myocardium (p=0.01), and increased fractional shortening (FS) (p>0.05) on POD 14, 21, and 28 by echocardiography. There were no significant differences in immunogenic response as determined by TNF⍺, IL6, CD86, or CD163 levels (p>0.05 for all) in the hearts. Biodistribution of fluorophore-conjugated ECM demonstrated localized epifluorescence in the heart after I/M injection, without significant peripheral end organ epifluorescence. Proteomic analysis of ischemic and perfused myocardium from control and ECM-treated hearts using LC-MS/MS (n=3/group) detected significant changes in proteins involved in cardiomyocyte contractility and fatty acid metabolism. These findings suggest that 3D ECM particles induce recovery of ischemic myocardium, by upregulating protein networks involved in cellular contractility and metabolism. Taken together, 3D ECM particles represent a promising therapy for MI, and warrant confirmatory studies in a high-fidelity large animal model.
ISSN
1522-1539
Published In/Presented At
Broadwin, M., Angelo, K. S., Petersen, M., Teixeira, R. B., Harris, D. D., Stone, C. R., Xu, C., Kanuparthy, M., Sellke, F. W., Morgan, J., & Abid, M. R. (2024). Lab-grown, 3D Extracellular Matrix Particles Improve Cardiac Function and Morphology in Myocardial Ischemia. American journal of physiology. Heart and circulatory physiology, 10.1152/ajpheart.00581.2024. Advance online publication. https://doi.org/10.1152/ajpheart.00581.2024
Disciplines
Medicine and Health Sciences
PubMedID
39705507
Department(s)
Department of Surgery, Fellows and Residents
Document Type
Article