Review
Copyright ©The Author(s) 2023.
World J Stem Cells. Apr 26, 2023; 15(4): 165-181
Published online Apr 26, 2023. doi: 10.4252/wjsc.v15.i4.165
Table 1 The mechanism of extracellular vesicles in the regeneration medicine
Source of EVs
Mechanism
KidneyMSC-EVsInhibiting oxidation, apoptosis, and inflammation
HLSC-EVsRegulating angiogenesis, the cell cycle, regeneration, autophagy, proliferation[36-38,46]
BMSC-EVs
Liver diseasehiPSCs-EVsInhibiting hepatocyte apoptosis
Hepatocyte-EVsSupporting hepatocyte function
MSC-EVsPromoting angiogenesis
Reducing inflammatory responses[48-53]
Cardiac muscleESCs-EVsVascularization
iPSCs-EVsAmelioration of apoptosis and hypertrophy
MSCs-EVsPromoting cell proliferation and migration[55-60]
CDCs-EVs
BMSC-EVs
TendonBMSC-EVsModulating macrophage phenotypes
ADSC-EVsAnti-inflammatory reaction
Enhancing proliferation, migration, tenogenic differentiation of TSCs
Regulating angiogenesis
Modulating immune responses[62-68]
Wound healingBMSC-EVsPromoting re-epithelialization
ADSC-EVsPromoting collagen maturity and angiogenesis
hENSC-EVEnhancing cell proliferation and migration[69-74]
HUVECs-EVs
iPSC-EVs
Tooth and periodontal tissueBMSC-EVsModulating the inflammatory immune response
ADSC-EVsEnhancing cell proliferation and migration
DPSC-EVsPromoting odontogenic differentiation
DFC-EVsStem cell recruitment[76-83]
PDLSC-EVs
HERS-EVs
SC-EVs
NerveSKP-SC-EVsMediating axon regeneration
BMSC-EVsRegulating the phenotype of Schwann cells
ADSC-EVsPromoting angiogenesis
GMSC-EVsRegulating inflammatory reactions[84-94]
BoneADSC-EVsAngiogenesis
BMSC-EVsOsteoblast proliferation
SMSC-EVsIntercellular communication
PRP-EVsImmune regulation[96-104]
EVs: Extracellular vesicles; MSCs: Mesenchymal stem cells; HLSC: Human liver stem cells; hiPSCs: Human-induced pluripotent stem cells; ESCs: Embryonic stem cells; iPSCs: Induced pluripotent stem cells; CDCs: Cardiosphere-derived cells; hENSC: Human Endometrial stem cells; DPSC: Dental pulp stem cells; DFC: Dental follicle cell; PDLSC: Periodontal ligament stem cells; PRP: Platelet-rich plasma; SMSC: Synovium mesenchymal stem cells; HERS: Hertwig’s epithelial root sheath; BMSC: Bone marrow mesenchymal stem cell; ADSC: Adipose stem cells; GMSC: Gingiva-derived mesenchymal stem cell; SKP-SC: Skin-derived precursor Schwann cells; TSC: Trophoblast stem cells.
Table 2 Extracellular vesicles investigated in clinical studies
Research title
Interventions
Status
Treatment of Patients with Bone Tissue Defects Using Mesenchymal Stem Cells Enriched by Extracellular VesiclesMSCs enriched by extracellular vesicles Not yet recruiting
Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for ARDS Bone Marrow MSC Derived Extracellular Not yet recruiting
Efficacy of Platelet- and Extracellular Vesicle-rich Plasma in Chronic Postsurgical Temporal Bone Inflammations Plateletand extracellular vesicle-rich plasma Completed
Use of Autologous Plasma Rich in Platelets and Extracellular Vesicles in the Surgical Treatment of Chronic Middle Ear Infections Plateletand EVs-rich plasma Recruiting
Extracellular Vesicle Infusion Treatment for COVID-19 Associated ARDS ExoFlo Completed
Safety of Mesenchymal Stem Cell Extracellular Vesicles (BMMSC-EVs) for the Treatment of Burn Wounds Drug: AGLE-102 (BMMSC-EVs) Not yet recruiting
Treatment of Non-ischemic Cardiomyopathies by Intravenous ExtracellularVesicles of CardiovascularProgenitor CellsExtracellular vesicle-enriched secretome of cardiovascular progenitor cells differentiated from induced pluripotent stem cells Not yet recruiting
Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for Mild-to-Moderate COVID-19: A Phase II Clinical Trial Drug: ExoFlo. Bone Marrow Mesenchymal Stem Cell Derived Extracellular VesiclesNot yet recruiting
A Safety Study of IV Stem Cellderived Extracellular Vesicles (UNEX-42) in Preterm Neonates at High Risk for BPD UNEX-42 is a preparation of extracellular vesicles that are secreted from human bone marrow-derived mesenchymal stem cells suspended in phosphate-buffered salineTerminated
ExoFlo™ Infusion for Post-Acute COVID-19 and Chronic Post COVID-19 Syndrome Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Not yet recruiting
Study of ExoFlo for the Treatment of Medically Refractory Ulcerative Colitis ExoFlo. Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesiclesRecruiting
Study of ExoFlo for the Treatment of Medically Refractory Crohn's DiseaseExoFlo. Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesiclesRecruiting
Bone Marrow Mesenchymal Stem Cell Derived EVs for COVID-19 Moderate-to-Severe ARDS: A Phase III Clinical Trial EXOFLO. Bone Marrow Mesenchymal Stem Cell Derived EVsRecruiting
Pilot Study of Human Adipose Tissue Derived Exosomes Promoting Wound Healing Adipose tissue derived exosomes Not yet recruiting
Exosome Effect on Prevention of Hairloss Placental Mesenchymal Stem Cells-derived ExosomeRecruiting
Expanded Access for Use of ExoFlo in Abdominal Solid Organ Transplant Patients Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment Not yet recruiting
Safety of Injection of Placental Mesenchymal Stem Cell Derived Exosomes for Treatment of Resistant Perianal Fistula in Crohn's PatientsPlacenal MSC derived exosomesActive, not recruiting
Safety and Efficacy of Injection of Human Placenta Mesenchymal Stem Cells Derived Exosomes for Treatment of Complex Anal Fistula Placenta MSCs derived exosomes Recruiting
Safety and Tolerability Study of MSC Exosome Ointment Exosome ointment Completed
The Pilot Experimental Study of the Neuroprotective Effects of Exosomes in Extremely Low Birth Weight Infants Exosomes derived from MSCsNot yet recruiting
ARDS: Acute Respiratory Distress Syndrome; MSC: Mesenchymal stromal cells; COVID-19: Coronavirus disease 2019; EVs: Extracellular vesicles.