Table 1.
The therapeutic effect of extracellular vesicles in preclinical osteoarthritis models
| Cell types | EV characterization methods | Main cargo | Animal models | Results | References |
|---|---|---|---|---|---|
| Human embryonic stem cells | WB (CD81, TSG101, ALIX) | Not mentioned | Surgical defect on trochlear grooves of the distal femurs osteochondral model in rats (1.5 mm diameter, 1 mm depth) | Hyaline cartilage formation characterized by uniform distribution of high amounts of glycosamninoglycan (GAG) and type II collagen, and low amount of type I collagen | [57] |
| Synovial mesenchymal stem cells (SMSCs) | WB (CD9, CD63, CD81, ALIX) | miR-140-5p | OA induced by medial meniscus surgery in rats | Prevention of early OA and prevented the severe damage to knee articular cartilage with increased type II collagen deposition | [54] |
| H1 human ES cell line | WB (CD9, CD63) | Not mentioned | OA induced by medial meniscus surgery in mice | Milder OA pathology such as roughened articular surface fibrillations below the superficial layer and some loss of lamina, with increased collagen II and decreased ADAMTS5 expression. | [55] |
| iPSCs- and synovial membrane- derived MSCs | WB (CD9, CD63, TSG101) | CD9, CD63 and TSG101 | Collagen-induced OA model in mice |
Re-formation of hyaline features with a smooth cartilage surface, regular cellular organization, and normal proteoglycan content. Decreased collagen I in animals treated with iMSC-Exos or SMMSC-Exos |
[56] |
| E1-MYC 16.3 human ESC- derived mesenchymal stem cells | WB (CD81, TSG101, ALIX) | Not mentioned | Surgical defect created on the trochlear grooves of the distal femurs osteochondral model in rats (1.5 mm diameter, 1 mm depth) |
Tissue regeneration deposition of s-GAG and type II collagen. Improved surface regularity and integration with the host cartilage |
[34] |
| Murine Bone marrow mesenchymal stem cells | FC (CD9, CD29, CD44, CD81, SCA-1), NTA | Not mentioned | Collagenase induced OA model in mice | Protection against osteoarthritic damages via anti-apoptotic role | [58] |
| Bone marrow mesenchymal stem cells | FC (CD63, CD44, CD73) | Not memtioned | Surgical defect created on rounded trephine grooves osteochondral model in dogs (3 mm diameter, 1 mm depth) | Marked regeneration of cartilage tissues | [59] |
| Human Bone marrow mesenchymal stem cells | NTA TEM (Transmission electron microscope) | miR-92a-3p | Collagenase induced OA model in mice |
The proliferation of chondrocytes Increased the matrix gene expression in MSCs and PHCs. miR-92-3p-mediated inhibition of WNT5A was shown. |
[60] |
| Mice Bone marrow mesenchymal stem cells | NTA, TEM, FC (CD9, CD29, CD44, CD81, SCA-1) | Not memtioned | Collagenase induced OA model in mice |
Induced a fewer plasmablasts and more Breg-like cells in lymph nodes. Induced an anti-inflammatory role on T and B cells |
[61] |
| Human Infrapatellar fat mesenchymal stem cells | NTA, TEM, WB (CD9, CD63, CD81) | miR-100-5p | Cutting the medial meniscus OA model in mice |
Protected articular cartilage from damage and ameliorated gait abnormality miR100-5p-mediated inhibition of mTOR-autopahgy pathway was shown |
[62] |
| Human Amniotic fluid stem cells | WB (CD9, CD63, CD81, Rab5, HGF, TGF- β, IDO) | Not mentioned | MIA induced OA in rats |
Enhanced pain tolerance and improved histological scores. Restoration of cartilage with surface regularity and the characteristic of hyaline cartilage. |
[63] |
Abbreviations: ADAMTS a disintegrin-like and metalloproteinase with thrombospondin motifs; ESCs: embryonic stem cells; FC: flow cytometry; HGF: hepatocyte growth factor; IDO: indoleamine-pyrrole 2,3-dioxygenase; iPSCs: induced pluripotent stem cells; MIA: monoiodoacetate; MSCs: mesenchymal stem cells; mTOR: mammalian target of rapamycin; NTA: nanoparticle tracking analyzer; PHC: primary human chondrocyte; S-GAG: sulfate-glycosaminoglycan; TEM, transmission electron microscopy; TGF: transforming growth factor; TSG101: tumor susceptibility gene 101; WB: western blot