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Table 1 The therapeutic effect of extracellular vesicles in preclinical osteoarthritis models

From: Therapeutic potential of stem cell-derived extracellular vesicles in osteoarthritis: preclinical study findings

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]
  1. 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