TABLE 1.
In vitro studies of MSC exosomes in other skin conditions.
| Source of exosomes | Isolation protocol | In vitro model | Disease | Signaling pathway and proteins involved | Outcomes | References |
| hUC-MSCs | The culture medium was processed using a series of centrifugation steps (300 g for 10 min, 2,000 g for 10 min and 10,000 g for 30 min). Exosomes were collected via ultracentrifugation at 100,000 g for 70 min | H2O2- stimulated primary keratinocyte culture | Oxidative stress | ↓NRF2 Keap1, HO-1 and NQO1 (NRF2 defense system) | ↓ROS generation and DNA damage ↓Aberrant calcium signaling ↓Mitochondrial changes | Wang et al., 2020 |
| hUC-MSCs | The culture medium was successively centrifuged at 400 g for 10 min, 2,000 g for 30 min and 10,000 g for 60 min. The supernatant was passed through a syringe filter (0.22 μm) and centrifuged at 100,000 g for 120 min to pellet exosomes. The pellet was washed and then centrifuged for another 120 min at the same high speed | UV-irradiated HDFs | Rejuvenation | ↑Collagen I, elastin and fibronectin ↓MMP-1 | Suppressive effects against UV-induced damage | Zhang Y. et al., 2020a |
| hUC-MSCs | The culture medium was centrifuged at 300 g for 10 min and 16,500 g for 30 min and then filtered through a 0.22 μm filter. The final supernatant was then ultracentrifuged at 100,000 g for 70 min to pellet exosomes. The pellet was filtered through a 0.22 μm filter and centrifuged at the same speed | Dendritic cells HaCaTs | Psoriasis | ↓IL-23 secretion ↓STAT3/pSTAT3 ↓IL-17, IL-23 and CCL20 | Suppressed dendritic cell maturation and activation ↓Inflammatory responses | Zhang Y. et al., 2020b |
| hBM-MSCs | The culture medium was centrifuged at 2,000 g for 30 min. The supernatant was passed through a 0.2 μm filter, mixed with Total Exosome Isolation Reagent (Invitrogen/Thermo Fisher Scientific), incubated overnight and centrifuged at 10,000 g for 1 h | Peripheral blood mononuclear cells | aGVHD | ↓Blocked T cell activation ↑miR-125a-3p | Immunoregulatory effects | Fujii et al., 2018 |
| hBM-MSCs | The culture medium was centrifuged 200 g for 10 min, 2,000 g for 20 min, 10,000 g for 30 min and 110,000 g for 7 h at 4°C, followed by filtration using a 0.22 μm filter. The culture supernatant was collected and ultracentrifugation was performed with the same sequential centrifugation procedure. The pellet was washed twice and then filtered through the 0.22 μm filter | Peripheral blood mononuclear cells | cGVHD | Blocked Th17 differentiation ↑Improved Treg phenotype | Regulatory effects on cGVHD effector cells | Lai et al., 2018 |
| hESC-MSCs | The culture medium was 0.22-μm filtered and concentrated 100 × for exosomes by tangential flow filtration (MWCO 100 kDa) | CD4+ T cells | GVHD | ↑Polarization of CD4+ T cells to CD4+ CD25+ FoxP3+ in the presence of allogenic CD11c+ cells | Immunoregulatory effects | Zhang W. et al., 2018a |
| BM-MSCs | The culture medium was filtered through a 0.22 μm pore size membrane and subjected to three continuous centrifugations at 300 g (10 min), 1,200 g (30 min) and 10,000 g (45 min). Then the supernatant was concentrated using 100 kDa Amicon® filter and exosomes were isolated with Exoquick TC kit according to the protocol | Melanoma murine cells | Melanoma | Not characterized | TRAIL exosomes induced higher apoptosis rate compared to non-modified exosomes | Shamili et al., 2018 |
| irUC-MSCs | Sequential centrifugations. Not specified | Melanoma cell line A375 | Melanoma | Not characterized | ↓Cell survival rate | de Araujo Farias et al., 2018 |
| BM-MSCs | The culture medium was centrifuged at 300 g for 10 min, at 1,500 g for 20 min and finally at 2,500 g for 20 min. The supernatant was filtered through a 0.2 μm syringe filter and ultracentrifuged at 100,000 g for 60 min. Pellets were washed and ultracentrifuged again | hDP-cells | Hair growth | ↑AKT phosphorylation ↑Bcl2 ↑VEGF and IGF-1 | ↑Proliferation and migration ↑Hair growth | Rajendran et al., 2017 |
| hUC-MSCs | Exosomes were isolated using exoEasy Maxi kit. Prefiltered culture medium was mixed with a binding buffer and added to the exoEasy membrane affinity column to bind the exosomes to the membrane. After centrifugation, the flow-through was discarded and wash buffer was added to the column. After another centrifugation and discarding the flow-through, the vesicles were eluted by adding elution buffer to the spin column, and the eluate was collected by centrifugation | HDFs Abdominal skin tissue (ex vivo) | Rejuvenation | ↓MMP1 | ↑Proliferation and collagen synthesis (in vitro) ↑Collagen I and elastin synthesis (ex vivo) | Kim et al., 2017 |