RETRACTED ARTICLE:Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway

Abstract

Background: Mesenchymal stem cells (MSCs) are suspected to exert neuroprotective effects in brain injury, in part through the secretion of extracellular vesicles like exosomes containing bioactive compounds. We now investigate the mechanism by which bone marrow MSCs (BMSCs)-derived exosomes harboring the small non-coding RNA miR-29b-3p protect against hypoxic-ischemic brain injury in rats. Methods:We established a rat model of middle cerebral artery occlusion (MCAO) and primary cortical neuron or brain microvascular endothelial cell (BMEC) models of oxygen and glucose deprivation (OGD). Exosomes were isolated from the culture medium of BMSCs. We treated the MCAO rats with BMSC-derived exosomes in vivo, and likewise the OGD-treated neurons and BMECs in vitro. We then measured apoptosis-and angiogenesis-related features using TUNEL and CD31 immunohistochemical staining and in vitro Matrigel angiogenesis assays. Results: The dual luciferase reporter gene assay showed that miR-29b-3p targeted the protein phosphatase and tensin homolog (PTEN). miR-29b-3p was downregulated and PTEN was upregulated in the brain of MCAO rats and in OGD-treated cultured neurons. MCAO rats and OGD-treated neurons showed promoted apoptosis and decreased angiogenesis, but overexpression of miR-29b-3p or silencing of PTEN could reverse these alterations. Furthermore, miR-29b-3p could negatively regulate PTEN and activate the Akt signaling pathway. BMSCs-derived exosomes also exerted protective effects against apoptosis of OGD neurons and cell apoptosis in the brain samples from MCAO rats, where we also observed promotion of angiogenesis.Conclusion: BMSC-derived exosomal miR-29b-3p ameliorates ischemic brain injury by promoting angiogenesis and suppressing neuronal apoptosis, a finding which may be of great significance in the treatment of hypoxic-ischemic brain injury.

MiR-150-5p-modified Bone Marrow Mesenchymal Stem Cells Derived Exosomes Ameliorate Osteonecrosis of Femoral Head by Promoting Endothelial Cell Angiogenesis

“…HIF-1α modi ed rabbit BMSC exosomes induced neovascularization by promoting the HUVEC cell ability, migration, and tube formation [32]. BMSCs have been shown to transfer miR-29b-3p into brain microvascular endothelial cells and enhance angiogenesis, resulting in amelioration of ischemic brain injury [33]. In accordant with previous studies, our results indicated miR-150-5p modi ed BMSC exosomes promoted the migration and tube formation of HUVECs.…”

Exosomes Secreted From Bone Marrow Mesenchymal Stem Cells Attenuate Oxygen-Glucose Deprivation/Reoxygenation-Induced Pyroptosis in PC12 Cells by Promoting AMPK-Dependent Autophagic Flux

“…As an important component of paracrine signaling in stem cells, exosomes appear to be promising candidates for repairing tissue injury in place of stem cells (Lazar et al, 2018 ; Williams et al, 2020 ). Previous studies have found that BMSC-Exos can promote nerve function and improve the nervous system in ischemic stroke (Deng et al, 2019 ; Xiao et al, 2019 ; Hou et al, 2020 ; Safakheil and Safakheil, 2020 ), but the specific mechanism remains to be explored. In the current study, TEM, NanoSight NTA, and the surface marker proteins confirmed that the BMSC-Exos were successfully isolated and met international standards (Théry et al, 2018 ).…”

“…Recent studies have demonstrated that exosomes secreted from BMSCs (BMSC-Exos) may play important roles in the effective biological performance of BMSCs (McBride et al, 2017 ; Lazar et al, 2018 ). Moreover, BMSC-Exos affect the biological characteristics of target cells through their interaction with specific ligand receptors, the transfer of receptors between cells, and the transfer of proteins and RNAs to target cells (Hou et al, 2020 ). Moreover, without any cytological characteristics such as proliferation and differentiation of BMSCs, BMSC-Exos have relatively stable biological characteristics, which reduce the risk of BMSC transplantation and make it possible to replace BMSCs for more effective treatment of cerebral I/R injury.…”

Exosomal microRNAs derived from mesenchymal stem cells: cell-to-cell messages

“…Because of the ability to transfer the contents of MSCderived exosomes (especially their miRNAs) to neighboring cells or to enable their circulation around the human body, MSC exosomes could influence the pathogenesis and progression of diseases [117][118][119][120]. There have been reports implicating the role of MSC-derived exosomal miRNAs in the field of neurodegenerative disease, especially in Alzheimer's disease [121], and also in stroke models.…”