Abstract
Marrow-isolated adult multilineage inducible (MIAMI) cells are a primitive mesenchymal stem/stromal cell subpopulation with plasticity and immunomodulatory properties. This study characterized MIAMI cell-derived extracellular vesicles (MIA-EVs) and evaluated their identity and activity in regenerative, inflammatory, oncology-related, and osteoarthritis (OA) models.
MIAMI cells expressed PDGFRB, CDX2, and TERT. MIA-EVs were isolated by ultracentrifugation and analyzed by nanoparticle tracking, electron microscopy, flow cytometry, and growth factor and miRNA profiling. Function was tested in keratinocyte wound repair, osteosarcoma proliferation, macrophage polarization, chondrocyte–synoviocyte co-culture, and a rat OA model.
This work reports the first isolation and characterization of MIA-EVs. They displayed nanoscale size, vesicular morphology, EV markers, and efficient uptake. Cargo included IGFBP-1, HGF, VEGF-D, and miRNAs linked to survival, regeneration, and immune regulation. Across naïve, irradiated, and cytokine-primed conditions, MIA-EVs retained a conserved 15-miRNA backbone while conditioning altered pathway weighting. Compared with MSC-EVs, they shared a mesenchymal miRNA core but showed broader regenerative and immune-regulatory connectivity.
MIA-EVs promoted keratinocyte wound repair, reduced osteosarcoma growth, induced context-dependent macrophage responses, and modulated inflammatory and matrix-remodeling genes in OA co-culture. In vivo, both EV types improved pain behaviors and increased collagen-associated staining, but MIA-EVs did not show OA-specific superiority. These findings establish MIA-EVs as a molecularly defined, active cell-free platform requiring further potency, dosing, and long-term efficacy studies.