TABLE 3.
Functional tests on Perinatal cell-derived small extracellular vesicles (sEV) alone or compared to perinatal cell-conditioned medium (CM).
| Perinatal cell-derived small extracellular vesicles (sEV) | |||
|---|---|---|---|
| PnD | Functional in vitro tests | Outcome | Reference |
| hUC-MSC-sEV | (i) Cell differentiation assay | (i) hUC-MSC-sEV inhibited α-SMA and collagen I and III expression in HDF cultivated at high cell density. (ii) hUC-MSC-sEV restrict HaCaT and HDF proliferation at high cell densities, but promote cell proliferation at low densities. | (Zhang et al., 2016) |
| (ii) Cell proliferation assay | |||
| (i) Cell proliferation assay | hUC-MSC-sEV promoted the (i, ii) proliferation, (iii, v) migration, and (iv) tube formation of a HUVEC-derived cell line in a dose-dependent manner. | (Zhang et al., 2015) | |
| (ii) Cytotoxicity assay | |||
| (iii) Scratch assay | |||
| (iv) Tube formation assay | |||
| (v) Chemotaxis assay | |||
| (i) Cell proliferation assay | hUC-MSC-sEV promoted (i) the proliferation, (ii) migration and (iii) tube-formation of HUVEC. hUC-MSC-sEV contained Ang-2, and treatment with hUC-MSC-sEV enhanced the expression of the Ang-2 in HUVEC through exosome-mediated Ang-2 transfer. | (Liu et al., 2021) | |
| (ii) Chemotaxis assay | |||
| (iii) Tube Formation Assay | |||
| Perinatal cell-derived small extracellular vesicles (sEV) compared to perinatal cell-CM | |||
| PnD | Functional in vitro tests | Outcome | Reference |
| a) hUC-MSC-sEV | (i) Cell apoptosis assay | hUC-MSC-CM and hUC-MSC-sEV (i) decreased H2O2-induced cell apoptosis of HaCaT by inhibiting AIF and upregulating PARP-1 and poly ADP-ribose, (ii) increased HaCaT proliferation, in contrast to hUC-MSC-sEV-dp. (iii) hUC-MSC-CM improved the viability of HaCaT. (iv, vi) hUC-MSC-sEV and hUC-MSC-CM promoted cell migration relative to the hUC-MSC-sEV-dp. (vi) (v) ROS intensity in the hUC-MSC-sEV group and hUC-MSC-CM group was lower than in the control group. | (Zhao et al., 2020) |
| b) hUC-MSC-CM | (ii) Cell proliferation assay | ||
| (iii) Cell viability assay | |||
| (iv) Chemotaxis assay | |||
| (v) ROS generation assay | |||
| (vi) Scratch wound assay | |||
| (i) Cell proliferation assay | (i) hUC-MSC-sEV/Pluronic F-127 hydrogel promoted HUVEC proliferation better than hUC-MSC-sEV and hUC-MSC-CM. (ii) hUC-MSC-sEV and CM groups showed greater cell migration than the Pluronic F-127 hydrogel and control group. The hUC-MSC-sEV/Pluronic F-127 hydrogel group exhibited the best performance. | (Yang et al., 2020) | |
| (ii) Scratch wound assay | |||
| a) hDMSC-sEV | Cell cycle assay Cell differentiation assay Cell proliferation assay Scratch wound assay Senescence assay ROS generation assay | (i) hDMSC-sEV enhanced proliferation of HG aged HDF, (iv) increased their migration rate, (ii) promoted differentiation of HG-aged HDF into myofibroblasts (increased α-SMA and collagen I protein expression), (v) inhibited senescence associated β-galactosidase expression and (vi) inhibited ROS generation in HG aged HDF. hDMSC-CM improved (iii) proliferation and (iv) migration of HDF. The sEV blocker GW4869 reduced both effects, indicating that hDMSC-sEV in hDMSC-CM probably enhance the proliferation and migration abilities of HDF. | (Bian et al., 2020) |
| b) hDMSC-CM | |||
Abbreviations; Ang-2: angiopoietin-2, AIF: apoptosis-inducing factor, α-SMA: alpha-smooth muscle actin, CM: conditioned medium derived from hDMSC, hUC-MSC, HaCAT: immortalized human keratinocytes, HDF: human dermal fibroblast, hDMSC: human decidua mesenchymal stromal cells, HG: high glucose, hUC-MSC: human umbilical cord mesenchymal stromal cells, PARP-1: poly ADP, ribose polymerase 1, ROS: reactive oxygen species, sEV: small extracellular vesicles derived from hDMSC, hUC-MSC, sEV-dp: conditioned medium depleted from small extracellular vesicle. Perinatal cell-derived small extracellular vesicles (sEV).