RETRACTED ARTICLE: Endothelial progenitor cell-derived exosomes, loaded with miR-126, promoted deep vein thrombosis resolution and recanalization

Abstract

BackgroundDeep vein thrombosis (DVT) is caused by blood clotting in the deep veins. Thrombosis resolution and recanalization can be accelerated by endothelial progenitor cells. In this report, we investigated the effects of miR-126-loaded EPC-derived exosomes (miR-126-Exo) on EPCs function and venous thrombus resolution.MethodsIn vitro promotional effect of miR-126-Exo on the migration and tube incorporation ability of EPCs was investigated via transwell assay and tube formation assay. In addition, a mouse venous thrombosis model was constructed and treated with miR-126-Exo to clarify the therapeutic effect of miR-126-Exo by histological analysis. Lastly, this study predicted a target gene of miR-126 using target prediction algorithms and confirmed it by luciferase activity assay, RT-qPCR, and Western blot.ResultsTranswell assay and tube formation assay indicated that miR-126-Exo could enhance the migration and tube incorporation ability of EPCs. Moreover, in vivo study manifested enhanced thrombus organization and recanalization after miR-126-Exo treatment. Meanwhile, we identified that Protocadherin 7 as a target gene of miR-126.ConclusionsTo sum up, our results demonstrated that EPC-derived exosomes loaded with miR-126 significantly promoted thrombus resolution in an animal model of venous thrombosis, indicating exosomes as a promising potential vehicle carrying therapeutic molecules for DVT therapy.

Exosomes secreted by endothelial progenitor cells accelerate bone regeneration during distraction osteogenesis by stimulating angiogenesis

“…Recent studies have supported the use of exosomes as promising alternatives for stem cell therapy [37]. EPC-Exos have been demonstrated to protect endothelial function in kidney injury, acute lung injury, and sepsis models; promote deep vein thrombosis resolution and artery re-endothelialization; and induce angiogenesis in skin wound healing [25, 38–40]. We therefore evaluated the effects of EPC-Exos on osteogenesis and consolidation in a rat tibial DO model, with EPCs as positive control.…”

“…Only normal EPC-Exos were investigated in this study. The limitation of this study is that the reported advantages of exosomes for drug or RNA delivery [38, 43] were not considered in the present study; hence, EPC-Exos modified to stimulate both osteogenesis and angiogenesis warrant further investigation in future studies.…”

MiR‐205 promotes endothelial progenitor cell angiogenesis and deep vein thrombosis recanalization and resolution by targeting PTEN to regulate Akt/autophagy pathway and MMP2 expression

“…26 Our previous studies have demonstrated that miRNAs have a vital role in EPC function. 11,[27][28][29][30] Additionally, miR-205 has been shown to have different effects on angiogenesis and migration in different types of tumours. [32][33][34][35]42 Meanwhile, miR-205 promotes wound healing in human corneal epithelial cells.…”

“…Of note, angiogenesis and thrombolysis are crucial for thrombus recanalization. [11][12][13] Numerous studies have shown that endothelial progenitor cells (EPCs) are recruited to the thrombus to accelerate thrombus resolution and play a vital role in physiological and pathological neovascularization in adults. 12,[14][15][16] Moreover, EPCs can differentiate into endothelial cells to participate in angiogenesis and thus are a promising therapeutic approach for thrombus resolution as there is only limited success with the current treatment options.…”

“…[27][28][29][30] A recent study has also indicated that miR-126-loaded EPC-derived exosomes are a promising potential vehicle for DVT therapy. 11 Among the emerging miRNAs, miR-205 has an important impact on the progression of diseases, but it is a "double-edged sword" in diseases. Studies have shown that miR-205 can facilitate wound healing in human corneal epithelial cells, 31 while it promotes tumour angiogenesis and cancer cell proliferation and migration in human nasopharyngeal carcinoma, lung cancer, breast cancer and endometrial cancer.…”