The epigenetic landscape of mesenchymal stem cell and extracellular vesicle therapy

Mesenchymal stem cell (MSC) therapy shows great potential for treating tissue impairments and immune disorders. Epigenetic regulation is a core molecular signature that ensures long-lasting memory in MSC functional modulation and mediates therapeutic efficacy. Studies reveal that transplanted MSCs drive epigenetic changes in recipient cells, which contributes to restoration of organismal and microenvironmental homeostasis. Extracellular vesicles (EVs) derived from MSCs, including exosomes and apoptotic vesicles (apoVs), enable the transfer of epigenetic regulators, orchestrating intercellular epigenetic reprogramming and signaling modulation in both local and systemic microenvironments. Here, the epigenetic regulation of MSC and EV therapies is reviewed, together with current challenges, aiming to deepen the understanding of donor-recipient communication and inspire next-generation approaches to counteract tissue defects and diseases.