Decoding the Regenerative Extracellular Matrix of Acomys Mouse to Develop New ECM-Guided Therapies for Cardiac Repair
Description: Cardiovascular disease remains the leading cause of death worldwide because the adult mammalian heart lacks the capacity to regenerate after injury. Following myocardial infarction, cardiac repair occurs predominantly through maladaptive fibrosis, leading to structural remodeling and progressive heart failure. In contrast, the Acomys mouse (Spiny) is a rare mammalian model with preserved regenerative ability. Acomys exhibits superior ischemic tolerance, reduced fibrosis, enhanced angiogenesis, and reconstitution of coronary microvasculature after injury, demonstrating a regenerative phenotype rather than scar-driven repair. Prior studies in other regenerative models, including zebrafish and neonatal mice, have shown that extracellular matrix (ECM) composition strongly influences cardiomyocyte proliferation and tissue recovery. Preliminary data from our group indicate that cardiac ECM isolated from Acomys hearts improves cardiac function and reduces fibrosis following MI in Mus Musculus mice. Integrated single-cell transcriptomic profiling comparing Acomys (Acomys Dimidiatus) and Mus (Mus Musculus) hearts revealed differentially expressed matrisome genes enriched in pro-angiogenic and pro-reparative pathways, supporting the concept that the ECM itself is a key driver of regeneration. We propose to define how regenerative ECM signals can be leveraged to identify new therapeutic candidates for myocardial repair. These goals will be pursued through three Specific Aims: Aim 1: Evaluate Acomys cardiac ECM's therapeutic efficacy in enhancing cardiac function and reducing fibrosis post-MI. Aim 2: Define the extracellular matrix composition and matrikine signatures of the Acomys heart. Aim 3: Determine the regenerative potential of selected candidate proteins and peptides derived from Acomys cardiac extracellular matrix (ECM).
Funder: American Heart Association
Amount: $231,000
Funding type: fellowship
Funder scheme: Career Development Award
Start date: 2026-04-01
End date: 2029-03-31
Investigators: Parisa Shabani, Parisa Shabani
Institution: The Regents of the University of Michigan
Funded outputs count: 0
Funder award ID: 26CDA1597321
OpenAlex ID: G2201501359