Multilineage-differentiating stress-enduring (Muse) cells in ischemic heart disease. A systematic review of preclinical and clinical studies.
Review
Overview
abstract
BACKGROUND: Multilineage-differentiating stress-enduring (Muse) cells are endogenous pluripotent stromal cells with immunomodulatory and regenerative properties. Their ability to migrate to injured tissue and differentiate into multiple lineages has generated interest in ischemic heart disease (IHD). METHODS: We conducted a systematic review using four databases which searched through July 2025 to identify preclinical and clinical studies of Muse cells in acute myocardial infarction (AMI) or coronary artery disease (CAD). Two reviewers independently performed data extraction and risk-of-bias assessment. RESULTS: Seven studies met inclusion criteria: four preclinical and three clinical. Preclinical models consistently showed that Muse cells localized to the infarct border zone, reduced infarct size, improved ventricular function, limited remodeling, and enhanced angiogenesis. Gene expression confirmed differentiation toward cardiac and vascular lineages. No immune reactions or tumor formation were reported, even with allogeneic or xenogeneic cells. Clinical studies demonstrated increased circulating Muse cells after AMI or exercise, with greater mobilization linked to improved ventricular function and reduced remodeling. A first-in-human trial reported improved ejection fraction without adverse events after allogeneic Muse cell infusion. CONCLUSION: Available evidence suggests that Muse cells are safe and may support cardiac repair after ischemic injury. Larger randomized trials are needed to confirm efficacy and long-term safety. PROTOCOL REGISTRATION IDENTIFIER: CRD420251105256.
