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Uncovering the Regional and Cell Specific Bioactivity of Injectable ECM Biomaterials in MI through Spatial and Single Nucleus Transcriptomics

ABSTRACT: Myocardial infarctions (MI) affect 805,000 people per year in the United States. To mitigate the pathological effects of MI, we have developed and investigated pro-reparative decellularized extracellular matrix (ECM) hydrogels. However, no one has ever utilized single cell and spatially resolved transcriptomics to further probe how ECM can elicit pro-repair in an MI model. Thus, we utilize spatial transcriptomics and single nucleus RNA sequencing (snRNAseq) to further delineate the regional and cell-specific bioactivity of decellularized ECM hydrogels. ECM hydrogel subacute treatment induced cardiac resident macrophage preservation, fibroblast activation, increased vasculature development, and a cardiomyocyte development program. Similar findings of cardiomyocyte and vasculature development, alongside fibroblast development was found for chronic treatment. Thus, we depict the pro-reparative nature of decellularized ECM hydrogels on cardiac cell types and elucidate previously undiscovered therapeutic pathways, further demonstrating ECM’s potential as an MI therapy.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE262430 | GEO | 2025/08/19

REPOSITORIES: GEO

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