TABLE 3.
Application of perinatal cell-derived small extracellular vesicles (sEV) alone or compared to perinatal cells in in vivo animal models of skin wound healing. Time points indicated in the “Dosage” and “Outcome” columns mean days (d) or weeks (w) of/after treatment.
| Perinatal cell-derived small extracellular vesicles (sEV) | |||||
|---|---|---|---|---|---|
| PnD | Dosage | Application (carrier) | Wound type, animal | Outcome | References |
| hUC-MSC-sEV | 100 μg/cm2 | Subcutaneous injection | Burn 2nd degree, rat | hUC-MSC-sEV enhanced re-epithelization and promoted self-regulation of Wnt/β-catenin signaling during the tissue remodeling period of cutaneous regeneration compared to PBS control (w2, w4) | Zhang et al. (2016) |
| 100 μg/cm2 | Subcutaneous injection | Burn 2nd degree, rat | hUC-MSC-sEV promoted re-epithelization and angiogenesis compared to controls (PBS, fibroblast-Ex, d7). Proangiogenic effects were inhibited by interference of Wnt4 expression in hUC-MSC- sEV. | Zhang et al. (2015b) | |
| 318 μg/cm2 | Subcutaneous injection | Burn 2nd degree, rat | hUC-MSC-sEV accelerated wound closure and angiogenesis compared to control (PBS, d13). Overexpression of Ang-2 in hUC-MSC-sEV further enhanced therapeutic effects. Knockdown of Ang-2 in hUC-MSC-sEV abrogated these effects | (Liu et al., 2020) | |
| 127 µg/cm2 | Subcutaneous injection | Burn 2nd degree, mouse | hUC-MSC- sEV treated with blue light (455 nm) achieved better angiogenic effects than untreated hUC-MSC- sEV (d7) | Yang et al. (2019) | |
| 127 µg/cm2 | Topical injection (Pluronic F127 hydrogel) | Full-thickness, diabetic rat | hUC-MSC-sEV -hydrogel and hUC-MSC- sEV -PBS accelerated the wound closure rate and vascularization compared to controls (gel, PBS). hUC-MSC- sEV -hydrogel achieved better effects than hUC-MSC- sEV -PBS (d7, d10, d14) | Yang et al. (2020) | |
| hDMSC-sEV | 2.6 × 10^10 particles/cm2 on every 7th d for 4w | Subcutaneous injection | Full-thickness, diabetic mouse | hDMSC-sEV accelerated wound closure and collagen deposition compared to PBS controls (d14, d21) | Bian et al. (2020) |
| Perinatal cell-derived small extracellular vesicles (sEV) compared to perinatal cells | |||||
| PnD | Dosage | Application (carrier) | Wound type, animal | Outcome | References |
| a) hAMSC | 2,222; 22,222; or 222,222 cells/cm2 Dose of sEV not specified | a) Subcutaneous injection (collagen) (b-c) Topical (collagen) | Full-thickness, rat | hAMSC and hAMSC-sEV enhanced wound closure and epidermalization. hAMSC-miR-135a-sEV induced faster wound healing than hAMSC-sEV (d5). Higher cell dose achieved better results than lower cell dose | Gao et al. (2020) |
| b) hAMSC-sEV | |||||
| c) hAMSC-miR-135a-sEV | |||||
| a) hUC-MSC | 1.56 × 10^6 cells/cm2 | (a-b) Subcutaneous injection | Full-thickness, mouse | hUC-MSC-sEV attenuated full-thickness skin wounds by enhancing epidermal re-epithelialization and dermal angiogenesis compared to hUC-MSC (d7, d14) | Zhao et al. (2020) |
| b) hUC-MSC-sEV | 156 μg-sEV/cm2 | ||||
| a) hUC-MSC-sEV | 100 μg sEV/cm2 | Subcutaneous injection | Burn 2nd degree, rat | hUC-MSC and hUC-MSC-sEV similarly accelerated re-epithelialization and increased expression of CK19, PCNA, and collagen I compared to control (PBS, fibroblast, Fibroblast-sEV, d7, d14) via Wnt4 pathway. hUC-MSC-sEV reduced heat stress-induced apoptosis via activation of AKT pathway | Zhang et al. (2015a) |
| b) hUC-MSC | 0.5 × 10^6 cells/cm2 | ||||
Abbreviations; hAMSC, human amniotic membrane mesenchymal stromal cells; hAMSC-miR-135a, human amniotic membrane mesenchymal stromal cells overexpressing miR-135a; hDMSC, human decidua mesenchymal stromal cells; hUC-MSC, human umbilical cord mesenchymal stromal cells; sEV, small extracellular vesicles derived from hAMSC, hDMSC, hUC-MSC; miR-135a-sEV, sEV overexpressing microRNA135a.