Exosomes Derived from miR-126-modified MSCs Promote Angiogenesis and Neurogenesis and Attenuate Apoptosis after Spinal Cord Injury in Rats

Huang, Jiang-Hu; Xu, Yanfang; Yin, Xiao‐Ming; Lin, Fei-Yue

doi:10.1016/j.neuroscience.2019.10.043

Cited by 121 publications

(102 citation statements)

References 37 publications

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“…The experiment was repeated three times, with n = 7 in each group endothelial cells and cardiomyocytes shows the potential for induction of local neo-vascularization during cardiac injury, and furthermore, cardiomyocyte-derived exosomes carry a broad repertoire of miRNAs and proteins under conditions of glucose deprivation [52]. In another example, exosomes derived from miR-126-modified MSCs facilitated the angiogenesis and migration of human umbilical venous endothelial cells after spinal cord injury [53]. Besides, upregulation of miR-29b plays a promotive role in ischemiainduced angiogenesis [54], indicating that miR-29b-3p is a promising factor in the treatment of hypoxic-ischemic brain injury.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE:Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway

Hou¹,

Li²,

Zhao³

et al. 2020

J Neuroinflammation

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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.

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Section: Discussionmentioning

confidence: 99%

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

Hou¹,

Li²,

Zhao³

et al. 2020

J Neuroinflammation

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“…32 Additionally, Exos are responsible for the delivery of miRNAs to the central nervous system, because of their stability and higher transfection efficiency. 33 In the present study, we focused our attention on the potential effects of Exos-transferred miR-146a-5p, and the possible molecular mechanisms involved in this process. Lentivirus infection was successfully performed in BMSCs which were isolated from rats to overexpress miR-146a-5p.…”

Section: Discussionmentioning

confidence: 99%

<p>Exosomes Derived from MicroRNA-146a-5p-Enriched Bone Marrow Mesenchymal Stem Cells Alleviate Intracerebral Hemorrhage by Inhibiting Neuronal Apoptosis and Microglial M1 Polarization</p>

Duan

Wang

Cao

et al. 2020

DDDT

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Introduction: Intracerebral hemorrhage (ICH) is a devastating type of stroke with high mortality, and the effective therapies for ICH remain to be explored. Exosomes (Exos) have been found to play important roles in cell communication by transferring molecules, including microRNAs (miRNAs/ miRs). MiRNAs are critical regulators of genes involved in many various biological processes and have been demonstrated to aggravate or alleviate brain damages induced by ICH. The aim of the present study was to investigate the effect of Exos derived from miR-146a-5p-enriched bone marrow mesenchymal stem cells (BMSCs-miR-146a-5p-Exos) on experimental ICH. Methods: ICH was induced in adult male Sprague-Dawley rats by an intrastriatal injection of collagenase type IV. At 24 h after surgery, Exos were administrated. For detecting apoptotic cells, TUNEL staining was performed using an in situ Cell Death Detection Kit. Fluoro-Jade B staining was performed to detect degenerating neurons. Immunofluorescence assay was performed to detect the expression of myeloperoxidase (MPO) and OX-42. The binding of miR-146a-5p and its target genes was confirmed by luciferase reporter assay. Results: At 24 h after surgery, BMSCs-miR-146a-5p-Exos administration significantly improved neurological function, reduced apoptotic and degenerative neurons, and inhibited inflammatory response. Furthermore, miR-146a-5p-enriched Exos obviously inhibited the M1 polarization of microglia after ICH in rats, accompanied by the reduced expression of pro-inflammatory mediators releasing by M1 microglia including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1). Finally, we observed that miR-146a-5p directly targeted interleukin-1 receptor-associated kinase1 (IRAK1) and nuclear factor of activated T cells 5 (NFAT5), which contributed to the inflammation response and the polarization of M1 microglia/macrophages. Conclusion: We demonstrated that miR-146a-5p-riched BMSCs-Exos could offer neuroprotection and functional improvements after ICH through reducing neuronal apoptosis, and inflammation associated with the inhibition of microglial M1 polarization by downregulating the expression of IRAK1 and NFAT5.

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“…Moreover, exosomes secreted from miRNA-29b-modified rat bone marrow-derived MSCs relieved SCI in rats, possibly by regulating proteins involved in neuronal regeneration, such as NF200, GAP-43, and GFAP[ 138 ]. Two consecutive studies assessed the effect of exosomes secreted from miRNA-126-modified rat bone marrow-derived MSCs on SCI in rat[ 139 , 140 ]. Huang et al[ 139 ] indicated that MSC-Exos miR-126 induce angiogenesis and neurogenesis, inhibit apoptosis, and promote functional recovery after SCI.…”

Section: Therapeutic Potential Of Msc-exos In Regenerative Medicinementioning

confidence: 99%

“…Two consecutive studies assessed the effect of exosomes secreted from miRNA-126-modified rat bone marrow-derived MSCs on SCI in rat[ 139 , 140 ]. Huang et al[ 139 ] indicated that MSC-Exos miR-126 induce angiogenesis and neurogenesis, inhibit apoptosis, and promote functional recovery after SCI. Yuan et al[ 140 ] indicated that MSC-Exos miR-126 protect the neurons of rats with SCI, stimulate axon regeneration, and improve the recovery of limb motor function after SCI, in part by activating ERK1/2, STAT3, and CREB and inhibiting RhoA expression.…”

Section: Therapeutic Potential Of Msc-exos In Regenerative Medicinementioning

confidence: 99%

Mesenchymal stem cell-derived exosomes: Toward cell-free therapeutic strategies in regenerative medicine

Yang

et al. 2020

WJSC

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Mesenchymal stem cells (MSCs) are multipotent stem cells with marked potential for regenerative medicine because of their strong immunosuppressive and regenerative abilities. The therapeutic effects of MSCs are based in part on their secretion of biologically active factors in extracellular vesicles known as exosomes. Exosomes have a diameter of 30-100 nm and mediate intercellular communication and material exchange. MSC-derived exosomes (MSC-Exos) have potential for cell-free therapy for diseases of, for instance, the kidney, liver, heart, nervous system, and musculoskeletal system. Hence, MSC-Exos are an alternative to MSC-based therapy for regenerative medicine. We review MSC-Exos and their therapeutic potential for a variety of diseases and injuries.

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Exosomes Derived from miR-126-modified MSCs Promote Angiogenesis and Neurogenesis and Attenuate Apoptosis after Spinal Cord Injury in Rats

Cited by 121 publications

References 37 publications

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

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

<p>Exosomes Derived from MicroRNA-146a-5p-Enriched Bone Marrow Mesenchymal Stem Cells Alleviate Intracerebral Hemorrhage by Inhibiting Neuronal Apoptosis and Microglial M1 Polarization</p>

Mesenchymal stem cell-derived exosomes: Toward cell-free therapeutic strategies in regenerative medicine

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