Table 1 MSCs-exos applications in tendinopathy
From: Mechanisms and therapeutic prospects of mesenchymal stem cells-derived exosomes for tendinopathy
Exosomes | Animal model OR in vitro experiments | Delivery method | Mechanisms | Biological effects |
|---|---|---|---|---|
BMSCs- exos | Rat patellar tendon defect model [49] Mouse tendon-bone reconstruction model [55] Rat medial collateral ligament (MCL) injury model [56] | Fibrin gel containing BMSCs-exos [49] Exosomes mixed with hydrogel [55] Exosome‐educated macrophages (EEMs) [56] | Promote the accumulation of CD146 + TSCs [49] Reduce M1 macrophages and proinflammatory factors (IL-1β and IL-6) in local tissues, increase M2 macrophages [55, 56] | Facilitate the proliferation and migration of TSCs [49] Decrease cell apoptosis, increase cell proliferation, reduce ECM deposition, and suppress excessive scar formation [55] Upregulate expression of collagen type I and III [56] |
ADSCs- exos | Mouse Achilles tendon injury and repair model [10] Rabbit rotator cuff tears (RCTs) model [57] Rat massive rotator cuff tear (MRCT) model [58] | ADSCs EVs-loaded collagen sheet [10] | Reduce NF‐κB activity, Il1b and Ifng expression; increase expression of Col1A1 and Col3A1 and thus decrease Mmp1, increase Scx and Tnmd [10] | Decrease muscle fatty infiltration [57] Promote anti-inflammatory, anti-apoptotic, and regenerative effects on rotator cuff tears [58] Modulate macrophage inflammatory response to reduce the early tendon inflammatory response after injury [10] |
TSC-exos | Rat Achilles tendon injury model [47] Rat Achilles tendon tendinopathy model [54] Rat patellar tendon defect model [59] | TSC-exos mixed in gelatin methacryloyl (GelMA, EFL-GM-60, 10%w/v) [47] Exosome injection [54] Isolated sEVs-mixed sodium alginate hydrogel [59] | Activate PI3K/AKT and MAPK/ERK1/2 signaling pathways Increase the number of CD163 + and IL-10 + cells; decrease the number of CCR7 + , IL-6 + , and Cox-2 + cells [47] Decrease MMP-3 and α-SMA expression, increase TIMP-3 and Col-1a1 [47, 54] Activate yes-associated protein (YAP) via the H19-PP1-YAP axis [59] | Promote effective healing of injured tendons [47] Increase capacity of biomechanical properties of ultimate stress and maximum loading [54] Promote proliferation, differentiation, migration, collagen deposition, and YAP localization [59] |
Purified exosome product (PEP) derived from plasma | Increase expression of genes linked to tendons (SCX, COL1A, COL3A1, TNMD, DCN, and MKX) [61] Increase expression of COL3A1, MMP2, MMP3, and MMP14; reduce expression of IL‐6 and TGF‐β [60] | Maintain capability of tenocyte migration and increase total collagen deposition, attenuate dexamethasone‐induced cellular apoptosis [61] Reduce inflammation and improve type III collagen expression [60] | ||
HUMSC-derived exosomes | Rat Achilles tendon injury adhesion model [62] | HUMSC-exos dissolved in PBS [62] | Deliver low-abundance miR-21a-3p, thus control p65 activity [62] | Reduce fibroblast proliferation and inhibit the expression of fibrosis genes: collagen III (COL III) and α-smooth muscle actin (α-SMA) in vitro [62] Relieve tendon adhesion [62] |