Therapeutic applications of mesenchymal stem cell-derived extracellular vesicles in pain management: A narrative review of emerging evidence and future directions

Table 2 Clinical trials evaluating mesenchymal stem cell-derived extracellular vesicle/exosome-based interventions for pain management

Study start year	Trial/study ID	Pain condition	Phase	Estimated enrollment	Intervention	Source
2024	NCT06431152	Knee osteoarthritis	Phase I	12	Intra-articular small EVs from umbilical cord MSCs	ClinicalTrials.gov
2024	NCT06466850	Osteoarthritis	N/A	20	Intra-articular MSC-derived exosomes	ClinicalTrials.gov
2021	NCT05060107	Knee osteoarthritis	Phase I	10	Single intra-articular MSC-derived exosome injection	ClinicalTrials.gov
2023	NCT04202783	Craniofacial neuralgia	Early phase (safety and efficacy)	100	Intravenous infusion of exosomes	ClinicalTrials.gov
2021	NCT04849429	Chronic low back pain (discogenic; intradiscal approach)	Phase I	30	Intradiscal injection of platelet-rich plasma with exosomes	[113]
2022 (approved year)	IRCT20210423051054N1	Knee osteoarthritis	Randomized, triple-blind clinical trial	31	Single intra-articular injection of placental MSC-EVs	[112]
-	ExoFlo interlaminar epidural safety study	Lumbar or cervical radiculopathy	Small open safety pilot study	10	Epidural injection of BM-MSC-EV isolate (ExoFlo); safety pilot	[114]

EVs: Extracellular vesicles; MSCs: Mesenchymal stem cells; N/A: Not applicable; MSC-EVs: Mesenchymal stem cell-derived extracellular vesicles; BM-MSC-EV: Bone marrow mesenchymal stem cell-derived extracellular vesicle.