Adipose-Derived Mesenchymal Stem Cell-Derived Extracellular Vesicles Rescue Tendon Injury in Rat via the miR-19 a/IGFBP3 Axis

Abstract

Purpose. Adipose-derived mesenchymal stem cells (ADSCs) are increasingly applied in tendon repair. However, the underlying mechanisms of ADSC-derived extracellular vesicles (EVs) in tendon healing are largely unknown. In this study, we investigated the effect of the EVs secreted by ADSCs on the recovery of tendon injuries and its potential mechanism. Materials and Methods. We injected ADSCs into the injured tendon, followed by the evaluation of the tissue morphology, tenocyte proliferation, and oxidative stress. Then, the injured tenocytes were treated with EVs secreted by ADSCs, and oxidative stress and proliferation of tenocytes in vitro were detected. After the overexpression and knockdown of miR-19a and its target protein IGFBP3, the oxidative stress and proliferation of tenocytes in vitro were assessed. Finally, the injured tendon was treated with EVs, and the tissue morphology and proliferation of the injured tendon in vivo were examined. Results. ADSC-derived EVs were found to inhibit oxidative stress and promote proliferation of tenocytes isolated from an injury model of rats. EVs were shown to carry miR-19a which regulated the expression of IGFBP3 through binding to 3 ′ UTR of IGFBP3 mRNA. In addition, IGFBP3 promotes oxidative stress and inhibits proliferation of tenocytes. Finally, we found that ADSC-derived EVs promoted tendon wound healing in vivo. Conclusions. Our data suggest that treatment with ADSC-derived EVs ameliorates tendon injury by inhibiting oxidative stress and promoting proliferation in tenocytes. miR-19a carried by ADSC-derived EVs regulates IGFBP3 expression through binding to its 3 ′ UTR.

Therapeutic Potential of Exosomes in Tendon and Tendon–Bone Healing: A Systematic Review of Preclinical Studies

“…After searching the six databases, a total of 1794 studies were found. Forty-five articles were included after screening and all of them were case–control studies [ 8 , 9 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 86 , 87 , 88 , 89 , 90 ]. Another article was included by searching the references of the included articles and review articles related to the topic [ 85 ].…”

“…All studies had a low risk of baseline characteristics under selection bias, random outcome assessment under detection bias, attrition bias, reporting bias, and other biases [ 8 , 9 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ]. All studies reported baseline characteristics of the animals used which included the species, age and gender of the animals, and the outcomes were randomly assessed [ 8 , 9 , 47 , 48 , 49 , 50 , 51 , 52 ,…”

“…It is significant to point out that current methods for exosome purification are immature and imperfect. Sometimes, other types of extracellular vesicles are present in purified exosomes, resulting in a diameter distribution that is not completely contained within the range of 30~150 nm [ 47 , 48 , 51 , 61 , 62 , 71 , 74 , 78 , 98 , 99 , 100 ]. So, for articles that focus on the effect of extracellular vesicles promoting tendon or tendon–bone healing, we examined the distribution of extracellular vesicle diameters.…”

“…Exosomes have been reported to play an effective therapeutic role in a variety of cancers [ 42 , 43 , 44 ], neurological diseases [ 45 ] and acute organ injuries [ 46 ]. In recent years, exosomes have also been proven to promote tendon and tendon–bone healing [ 8 , 9 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ].…”

Retracted: Adipose‐Derived Mesenchymal Stem Cell‐Derived Extracellular Vesicles Rescue Tendon Injury in Rat via the miR‐19 a/IGFBP3 Axis

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Manipulated or compromised peer review …”