Table 2.
Therapeutic Effects and Molecular Mechanisms of Exosomes Derived From MSCs for the treatment of OA and Osteochondral Defects Treatment In Vivo and In Vitro.
| Origin | Isolation methods | Subjects | Therapeutic effects and molecular mechanisms | References |
|---|---|---|---|---|
| Human MSCs (HuES9) | HPLC fractionation | In vivo: rat osteochondral defects created on the trochlear grooves of the distal femurs. In vitro: NM | In vivo: Exosome-treated defects showed enhanced gross appearance and improved histological scores than the contralateral PBS-treated defects. In vitro: NM | 59 |
| Human MSCs (E1-MYC 16.3) | Ultrafiltration | In vivo: rat osteochondral defects created on the trochlear grooves of the distal femurs. In vitro: PRAC |
In vivo: exosomes increased cellular proliferation and infiltration, enhanced matrix synthesis and a regenerative immune phenotype In vitro: CD73 in exosomes activated AKT and ERK signaling pathway |
58 |
| Human SMSCs | Ultrafiltration | In vivo: KOA rats induced by ACLT and MMT. In vitro: PHC | In vivo: SMSC-140-Exos prevented OA better than SMSC-Exos. In vitro: SMSC-140-Exos enhanced the proliferation and migration of ACs without damaging ECM secretion via RalA | 61 |
| Human MSCs | Density gradient ultracentrifugation | In vivo: KOA rats induced by type II collagenase. In vitro: PRAC treated with IL-1β | In vivo: MSCs exosomes promoted cartilage repair better than those knocking down lncRNA-KLF3-AS1. In vivo: lncRNA KLF3-AS1 enriched in exosomes promoted cell proliferation and suppressed apoptosis | 63 |
| Rat MSC | Extraction kit | In vivo: KOA rats induced by medial collateral ligament and MMT. In vitro: rat chondrocyte line (C5.18 cell) | In vivo: exosomes treated with TGF-β1 promoted cartilage repair better and miR-135b inhibitor inhibited the therapeutic effects. In vitro: TGF-β1 promoted chondrocyte proliferation by regulating Sp1 through miR-135b enriched in MSC exosomes | 64 |
| Human ESC-MSCs | Differential ultracentrifugation | In vivo: KOA mice induced by DMM. In vitro: PMACs treated with IL-1β | In vivo: protected cartilage and bone from degradation. In vitro: exerted similar chondroprotective and anti-inflammatory | 60 |
| Murine BMSCs | Differential ultracentrifugation | In vivo: KOA mice induced by type II collagenase. In vitro: PMAC treated with IL-1β | In vivo: impeded cartilage destruction and OA process. In vitro: maintained chondrocyte phenotype by increasing Col2a1 synthesis and decreasing ADAMTS5 expression | 38 |
| Human BMSCs | Differential ultracentrifugation | In vivo: KOA mice induced by type II collagenase. In vitro: human MSCs, normal and OA PHC | In vivo: MSC-92a-Exos inhibited the progression of early OA and prevented articular cartilage damage better than MSC-Exos. In vitro: MSC-92a-Exos promoted chondrocyte proliferation and matrix genes expression better, and targeted WNT5A expression | 65 |
| Human IPFP MSCs | ExoQuick™ (EQ) reagent kit (SBI) and ultrafiltration | In vivo: KOA mice induced by DMM in right knees. In vitro: PHC treated with IL-1β | In vivo: protected AC from damage and ameliorated gait abnormality; miR-100-5p in exosomes targeted mTOR pathway. In vitro: inhibited cell apoptosis, enhanced matrix synthesis, and enhanced autophagy level partially via mTOR inhibition | 37 |
| Human MSCs | Density gradient ultracentrifugation | In vivo: KOA mice induced by type II collagenase. In vitro: PMAC treated with IL-1β, KOA articular chondrocytes | In vivo: NM. In vitro: increased Col2a1 and aggrecan, and decreased MMP13 and RUX2 expression in KOA chondrocytes; attenuated apoptosis in KOA articular chondrocyte; LncRNA-KLF3-AS1 in exosomes targeted miR-206/GIT1 axis | 66 |
| Human ADSCs | Differential ultracentrifugation | In vivo: NM. In vitro: osteoblasts of osteoarthritic patients | In vivo: NM. In vitro: anti-inflammation, and downregulation oxidative stress and senescence in osteoblasts | 67 |
| Human BMSCs | Differential ultracentrifugation | In vivo: NM. In vitro: PMAC treated with TNF-α | In vivo: NM. In vitro: inhibited adverse effects of inflammation on cartilage homeostasis and promoted cartilage regeneration | 68 |
| Rabbit BMSCs | Ultrafiltration | In vivo: NM. In vitro: primary rabbit chondrocytes | In vivo: NM. In vitro: inhibited MS-induced apoptosis of chondrocytes via p38, ERK, and Akt pathways | 69 |
AC: articular cartilage; ACLT: anterior cruciate ligament transection; ADSCs: adipose-derived MSCs; DMM: destabilization of the medial meniscus; ECM: extracellular matrix; HPLC: high-performance liquid chromatography; IPFP: infrapatellar fat pad MSCs; KOA: knee OA; MMT: medial meniscus transection; MS: mitochondrial dysfunction; MSC: mesenchymal stem cells; MSC-92a-Exos: exosomes derived from BMSCs overexpressing miR-92a-3p; NM: not mentioned; OA: osteoarthritis; PHC: primary human chondrocytes; PMAC: primary mouse articular chondrocytes; PRAC: primary rat articular chondrocytes; SMSCs: synovial MSCs; SMSC-140-Exos: exosomes derived from SMSCs overexpressing miR-140-5p.