TABLE 3

Overview of regenerative function comparison studies between lEVs and sEVs

Therapeutic TargetEV SourceNon-EV RemovalFractionsaEV Marker EnrichmentReference
Kidney
In vitro: murine tubular epithelial cells
In vivo: acute kidney injury mouse model
Bone marrow MSCs3000 × gtEV-100K
lEV-10K
sEV-100K
lEV: CD29, CD44, CD73, CD105
sEV: CD63, CD9, CD29, CD44, CD73, CD105
(Bruno et al., 2017)
Kidney
In vitro: human umbilical vein endothelial cells
In vivo: acute kidney injury mouse model
Endothelial colony-forming cells2500 × glEV-20K
sEV-100K
lEV: Caveolin-1
sEV: TSG101, CD63
(Burger et al., 2015)
Kidney
In vitro: murine tubular epithelial cells
Bone marrow MSCs1500 × gHD-EV
MD-EV
LD-EV
HD-EV: CD29, annexin A2
MD-EV: CD63, CD81, CD29, integrin α5, annexin A2, HLA-1
LD-EV: none
(Collino et al., 2017)
Immune cells
In vitro: T- and B- cells
In vivo: Collagen-induced arthritis mouse model
Bone marrow MSCs300 + 2500 × g
Filter 0.22 μm
tEV-100K
lEV-18K
sEV-100K
lEV: Sca-1, CD44, CD29
sEV: CD9 and CD81, HSP70, TSG101, ALIX
(Cosenza et al., 2018)
Cartilage
In vitro: murine chondrocytes
In vivo: Collagen-induced arthritis mouse model
Murine bone marrow MSCs300 + 2500 × g
Filter 0.22 μm
lEV-18K
sEV-100K
lEV: CD29, CD44 and Sca-1
sEV: CD9, CD81
(Cosenza et al., 2017)
Neural tissue
In vitro: cortical neuron culture and dorsal root ganglia cultures
Menstrual MSCs200 + 2000 × gtEV-100K
lEV-10K
sEV-100K
lEV: CD73, CD90, CD105, integrin α1, CD63, HLA-1
sEV: CD63, TSG101, HSP70, HSP90
(Lopez-Verrilli et al., 2016)
Neural tissue
In vitro: dopaminergic neuron (suspension-like) culture
SHEDs cultured in a bioreactor300 + 2000 × glEV-20K
sEV-100K
(Jarmalavičiūtė et al., 2015)
Pancreas
In vivo: diabetes mouse model
Pathfinder cells1000 × glEV-16K
sEV-120K
lEV: Integrin-β1, CD40
sEV: CD9, CD63, CD81, TSG101, Rab5B, integrin β1
(McGuinness et al., 2016)
Endothelium
In vitro: human aortic endothelial cells
Plasma samples of chronic coronary syndrome patients and healthy controlsFilter 1 μm
Filter 0.2 μm
lEV-16K
sEV-100K
lEV: TSG101
sEV: TSG101, CD63, CD81
(Kränkel et al., 2020)
  • aEV fractions showing significant regenerative effects are marked in bold, whereas damaging effects are marked in italic and underlined. Total EV (tEV).