Table 2.
A summary of in vitro and in vivo studies of exogenous MSC-EVs for treating osteoporosis.
| Animal Model | Terminology | Source of EVs | Administration Route | EVs Cargos | Duration of Treatment | Time Point of Sacrifice | Target | Refs. |
|---|---|---|---|---|---|---|---|---|
| In vitro (steroid-related osteoporosis) |
EVs | AFSCs | In vitro model | Not revealed | 4 days (Dose not revealed) |
Not applicable | Related proteins (SIRT1, FoxO, Nrf2, p21, Galectin-3, AP-1 complex) |
[120] |
| OVX mice | Aptamer-functionalized exosomes | BMSCs | IV injection | miR-26a | 100 μg EVs, once per week for 2 months | endpoint of treatment | Not revealed | [119] |
| Healthy mice | Exosomes | BMSCs | IV injection | miR-29a | 100 μg EVs, twice per week for 2 months | endpoint of treatment | VASH1 | [91] |
| CBS+/− heterozygous mice | Exosomes | BMSCs | IV injection | lnc-H19 | 100 μg EVs, 3 times per week for 2 months | endpoint of treatment | miR-106a/Angpt1 | [93] |
| OVX rat | Exosomes | BMSCs | IV injection | miR-186 | 1013/mL EVs, once per week for 1 months | endpoint of treatment | Hippo signaling pathway | [86] |
| In vitro | Exosomes | BMSCs | In vitro model | Not revealed | Not revealed | Not revealed | MAPK signaling pathway | [121] |
| OVX rat | GPNMB-modified BMSC-EV | BMSCs | IV injection | GPNMB | 100 μg EVs, once per week for 2 months | endpoint of treatment | Wnt/β-catenin signaling pathway | [101] |
| Aged male mice (16 months old) |
EVs | hUCB | IV injection | miR-3960 | 100 μg EVs, once per week for 8 weeks | 1, 2 and 8 weeks after the first treatment | HOXA2 | [89] |
| OVX mice | EVs | hucMSCs | IV injection | CLEC11A | 100 μg EVs, once per week for 2 months | endpoint of treatment | Integrin α11 | [99] |
| In vitro | EVs isolated from OVX mice with agomiR-miR-29b-3p injection | BMSCs | In vitro model | miR-29b-3p | Not revealed | Not applicable | KDM5A/NF-kB pathway | [87] |
| OVX mice | Exosomes | WJ-MSCs | IP injection | miR-328-3p, miR-2110 | 0.5 mg/kg EVs, every 3 days for 6 weeks | endpoint of treatment | CHRD, TNF | [88] |
| OVX rat | sEV | BMSCs | Not revealed | miR-20a/BAMBI | 3 weeks (Dose not revealed) |
endpoint of treatment | BAMBI | [122] |
Abbreviation: OVX, ovariectomized; sEV, small extracellular vesicles; AFSC, amniotic fluid stem cells; BMSCs, bone marrow mesenchymal stem cells (BMSCs); hUCB, human umbilical cord blood; hucMSCs, human umbilical cord blood-derived mesenchymal stem cells; WJ-MSCs, Wharton’s jelly mesenchymal stem cells; SIRT1, Sirtuin 1; FoxO, class O of forkhead box transcription factors; Nrf2, nuclear factor erythroid 2-related factor 2; AP-1, activator protein 1; VASH1, vasohibin 1; Angpt1, angiopoietin 1; MAPK, mitogen-activated protein kinases; GPNMB, glycoprotein non-melanoma clone B; HOXA2, homeobox A2; CLEC11A, C-Type lectin domain containing 11A; KDM5A, lysine-specific demethylase 5A; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; CHRD, chordin; TNF, tumor necrosis factor; BAMBI, BMP and activin membrane bound inhibitor.