Bone marrow mesenchymal stromal cell-derived exosomes in knee osteoarthritis: Bridging mechanistic understanding to clinical applications

Table 3 Human studies of mesenchymal stromal cell-derived extracellular vesicles relevant to knee osteoarthritis

EV source	Indication/design	Intervention and comparator	Main outcomes	Key limitations
Placental MSC exosomes[83-85]	Bilateral KOA, triple-blind randomised placebo-controlled trial	Single intra-articular exosome injection to one knee, saline to contralateral knee	Good short-term safety; no significant advantage over saline in pain, function or MRI cartilage metrics	Single-dose regimen; short follow up; partial EV characterisation; no dose-finding
Umbilical cord MSC small EVs[86]	KOA, first-in-human open-label phase I study	Intra-articular small EVs, single or repeated dosing, no control group	Acceptable 12-month safety; symptomatic improvement; MRI signs of cartilage regeneration; evidence of M2-like macrophage polarisation	Non-randomised; small sample; potential placebo and regression effects
BM-MSC-derived EV product (for example, ExoFlo)[87,88]	Osteoarthritis and joint injuries, observational cohorts	Intra-articular injection, no formal comparator	Symptomatic improvement reported; no major acute toxicity	Non-randomised; heterogeneous pathology; limited EV characterisation; lack of long-term imaging and independent replication

EV: Extracellular vesicle; MSC: Mesenchymal stromal cell; KOA: Knee osteoarthritis; MRI: Magnetic resonance imaging; BM-MSC: Bone marrow mesenchymal stromal cell.