Table 2.
Published Studies on Biogenesis of mesenchymal stem cell-osteoblast (MSC-OB) lineage derived EVs in monocyte recruitment, polarization and function
| Source | Methods: isolated and identified | Specific Cargo | Target cells and Genes | Function | Signaling Pathway | References |
|---|---|---|---|---|---|---|
| Rat BMSC-EVs | ·Density‐gradient ultracentrifugation :2 subsequent centrifugations steps of 2500g for 15 minutes ·NTA, TEM and Western blot (CD63, CD81, HSP70 and Tsg101) |
- | ·Raw264.7 and rat peritoneal macrophages |
M2 polarization ↑ M1 polarization ↓ reduced the inflammation |
BMSC-EVs + LPS+ Raw264.7→NF‐κB p65 ↓ → AKT1 /AKT2 → M2 ↑, M1 ↓ →IL‐6, TNF‐α, IL‐1β ↓ |
Ruqin Xu, 2019 |
| Rat BMSC-EVs | · Utral centrifuged: 300g for 10 min, 2000g for 10 min. After centrifugation, 0.22 μm Steritop™ and Amicon ultra-15 spinning Filter Unit, the liquid was centrifuged at 100,000g for 60 min ·TEM, Western blot (CD9, CD63 and CD81) |
- | ·HUVECs and macrophages | M1 polarization ↓ secretion of proinflammatory factors by M1 macrophages↓. |
BMSC-EVs + HUVECs→ phosphorylation levels of VEGFR1 and VEGFR2 ↑, LATS1/2 and YAP1 ↓ BMSC-EVs→ M1 ↓ → TNF-α, IL-1β, IL-6, IL-8, and NOS-2 ↓ |
Yao Huang, 2020 |
| Mouse BMSC-EVs | ·Ultracentrifugation: 2000g for 30 min, 10,000g for 30 min, 100 000g for 70 min; ·Zeta View system, TEM and Western blot (CD81, TSG101, and CD9) |
- | ·Mouse Bone marrow-derived macrophages | M2 polarization ↑ M1 polarization ↓ |
BMSC-EVs→ M2 polarization ↑ →fibrocartilage and biomechanical property ↑ |
Youxing Shi, 2020 |
| Mouse BMSC-EVs | ·Filtration through a 0.22-μm filter and exosome isolation kit. ·TEM and flow cytometry (CD90) |
miR-124-3p | ·Mouse Bone marrow-derived macrophages · Ern1 |
M2 polarization ↑ | BMSCs containing miR-124-3p + macrophage →Ern1 expression ↓ → M2 ↑ | Ran Li, 2020 |
| Rat BMSC-EVs | ·Ultracentrifugation: 300g for 10 min, 2000g for 15 min, 10,000g for 30 min, and 100,000g for 70 min twice ·TEM, NTA and Western blot (CD9, CD63, TSG101, and Calnexin) |
miR-31a-5p | · Osteoclasts · E2F2, SAHF |
Osteoclasts numbers and function↑ |
miR‐31a‐5p→ E2F2 ↓ → SAHF assembly induces cellular aging→ osteoclastic numbers and function↑ | Rongyao Xu, 2018 |
| Human JMSC and BMSC-EVs |
·Ultracentrifugation: 100,000g for 3 h, 3000g for 15 min, mixed with ExoQuick-TC, then centrifuged at 1500g for 30 min. Western blot (CD63 and CD81) and NTA |
miR-223 | ·Human peripheral blood PBMC-derived macrophage pknox1 |
M2 polarization ↑ Enhances cutaneous wound healing |
miR-223 + BMSCs→ targeting pknox1→M2 polarization ↑ | Xiaoning He, 2019 |
| Mouse Osteoblast-EVs | ·Ultracentrifugation: 5000g for 10 min, 35,000g for 10 min, 100,000g for 70 min at 4 °C. ·Western blot (CD63) and TEM |
- | · Osteoclasts | Osteoclasts numbers and function↑ | Osteoblasts-EVs via RANKL-RANK → osteoclast formation↑ | Alfredo Cappariello, 2018 |
| Osteocyte-EVs | - | - | - | - | - |