Extracellular Vesicles at the Interface of Cancer Therapy and Regenerative Medicine: Biology, Bidirectional Roles, and Engineered Therapeutics.

Abstract

Extracellular vesicles (EVs), including exosomes and microvesicles, are nanoscale membrane-enclosed particles that transfer proteins, lipids, mRNAs, and microRNAs between cells. The same communication system is now being developed in two apparently opposing settings: mesenchymal stem/stromal cell (MSC)-derived EVs are explored as cell-free regenerative therapeutics, whereas tumor-derived EVs can promote metastasis, immune evasion, and treatment resistance while also serving as liquid-biopsy biomarkers. Rather than treating these studies separately, this review compares them along shared mechanistic axes: producer-cell identity and state, luminal cargo, membrane and surface composition (including the biomolecular corona), dose and administration route, biodistribution, and recipient-cell context. This cross-field perspective shows that angiogenesis, immunomodulation, matrix remodeling, and tissue tropism are not intrinsically regenerative or oncogenic; their consequences depend on where, how, and to which cells EV signals are delivered. We review EV biology and MISEV2023-aligned nomenclature, examine bidirectional regenerative and cancer-associated functions, and survey engineering strategies for cargo loading and surface modification together with plant-derived exosome-like nanovesicles. We further compare EVs with lipid nanoparticles, adeno-associated viruses, polymers, and virus-like particles, and discuss how engineering can improve potency and targeting while increasing manufacturing and characterization complexity. Finally, we address tumor-related safety considerations for regenerative EVs and the unresolved biological, technical, manufacturing, and regulatory questions that must be addressed for clinical translation.