# Bioengineered Cellular and Acellular Therapies for Ischemic Heart Disease in Clinically Relevant Models

## TL;DR

This review explores bioengineered therapies for heart disease, focusing on large animal models to improve clinical translation.

## Contribution

The paper emphasizes the use of large animal models to evaluate cellular and acellular therapies for ischemic heart disease.

## Key findings

- Stem cells, extracellular vesicles, and matrix-based strategies show promise in promoting heart tissue repair.
- Large animal models are critical for assessing the translational potential of these therapies.
- Clinical translation is hindered by issues like poor engraftment and arrhythmogenic risk.

## Abstract

Despite significant improvements in revascularization strategies and medical management, ischemic heart disease (IHD) remains the top cause of mortality and disability worldwide. The myocardium lacks regenerative capacity and consequently, recovery depends on re-establishing microvascular integrity and sustaining angiogenesis to preserve viable myocardium. Emerging and novel bioengineering approaches, such as stem cells, extracellular vesicles (EVs), and matrix-based strategies, seek to address this unmet need by promoting neovascularization and structural restoration. However, clinical translation remains limited by poor engraftment, product variability, and arrhythmogenic risk. Large animal models provide a clinically relevant platform to thoroughly investigate these interventions and ideally enhance their translational potential. This review discusses cellular approaches leveraging stem and progenitor cells and acellular modalities using extracellular vesicles, growth factors, or extracellular matrix-based scaffolds with an emphasis on large animal translational models and clinical trials.