Mesenchymal stem cell-derived exosome: a promising alternative in the therapy of Alzheimer’s disease

Guo, Mengtian; Yin, Zhenyu; Chen, Fanglian; Lei, Ping

doi:10.1186/s13195-020-00670-x

Cited by 114 publications

(78 citation statements)

References 162 publications

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“…Others release their vesicles as exosomes. Exosomes were found to deliver their contents to target cell by receptor-ligand binding, direct membrane fusion, and endocytosis [ 22 ]. They mediate intercellular communication by transporting miRNAs, proteins, cytokines, mRNAs, etc.…”

Section: Introductionmentioning

confidence: 99%

Exosomes derived from miR-26a-modified MSCs promote axonal regeneration via the PTEN/AKT/mTOR pathway following spinal cord injury

Chen

Tian

et al. 2021

Stem Cell Res Ther

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Background Exosomes derived from the bone marrow mesenchymal stem cell (MSC) have shown great potential in spinal cord injury (SCI) treatment. This research was designed to investigate the therapeutic effects of miR-26a-modified MSC-derived exosomes (Exos-26a) following SCI. Methods Bioinformatics and data mining were performed to explore the role of miR-26a in SCI. Exosomes were isolated from miR-26a-modified MSC culture medium by ultracentrifugation. A series of experiments, including assessment of Basso, Beattie and Bresnahan scale, histological evaluation, motor-evoked potential recording, diffusion tensor imaging, and western blotting, were performed to determine the therapeutic influence and the underlying molecular mechanisms of Exos-26a in SCI rats. Results Exos-26a was shown to promote axonal regeneration. Furthermore, we found that exosomes derived from miR-26a-modified MSC could improve neurogenesis and attenuate glial scarring through PTEN/AKT/mTOR signaling cascades. Conclusions Exosomes derived from miR-26a-modified MSC could activate the PTEN-AKT-mTOR pathway to promote axonal regeneration and neurogenesis and attenuate glia scarring in SCI and thus present great potential for SCI treatment. Graphical abstract

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Section: Introductionmentioning

confidence: 99%

Exosomes derived from miR-26a-modified MSCs promote axonal regeneration via the PTEN/AKT/mTOR pathway following spinal cord injury

Chen

Tian

et al. 2021

Stem Cell Res Ther

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“…Exosomes are nanosized vesicles with a phospholipid bilayer involved in cell-to-cell communication, cell signaling, and being able to alter cell or tissue metabolism at short or long distances in the body [ 20 , 21 ]. MSC exosomes enclose lipids (lipids or lipid rafts, cholesterol, sphingolipid ceramide, lipid raft marker protein-1, phosphoglycerides) and nucleic acids (such as miRNA, coding RNA, non-coding RNA, DNA) [ 22 – 24 ]. At the same time, they have common marker proteins on their surfaces, such as membrane proteins (CD9, CD63, CD81, CD82), proteins involved in the sorting and transport of intercellular complexes (Alix, Tsg101), membrane transport fusion eggs (GTPases, annexins, flotillin, Rab protein), and heat shock protein (HSP70, HSP90) [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Exosomes derived from human placental mesenchymal stem cells enhanced the recovery of spinal cord injury by activating endogenous neurogenesis

et al. 2021

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Background Spinal cord injury (SCI) is a debilitating medical condition that can result in the irreversible loss of sensorimotor function. Current therapies fail to provide an effective recovery being crucial to develop more effective approaches. Mesenchymal stem cell (MSC) exosomes have been shown to be able to facilitate axonal growth and act as mediators to regulate neurogenesis and neuroprotection, holding great therapeutic potential in SCI conditions. This study aimed to assess the potential of human placental MSC (hpMSC)-derived exosomes on the functional recovery and reactivation of endogenous neurogenesis in an experimental animal model of SCI and to explore the possible mechanisms involved. Methods The hpMSC-derived exosomes were extracted and transplanted in an experimental animal model of SCI with complete transection of the thoracic segment. Functional recovery, the expression of neural stem/progenitor cell markers and the occurrence of neurogenesis, was assessed 60 days after the treatment. In vitro, neural stem cells (NSCs) were incubated with the isolated exosomes for 24 h, and the phosphorylation levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinases (ERK), and cAMP response element binding (CREB) proteins were assessed by western blot. Results Exosomes were successfully isolated and purified from hpMSCs. Intravenous injections of these purified exosomes significantly improved the locomotor activity and bladder dysfunction of SCI animals. Further study of the exosomes’ therapeutic action revealed that hpMSC-derived exosomes promoted the activation of proliferating endogenous neural stem/progenitor cells as denoted by the significant increase of spinal SOX2+GFAP+, PAX6+Nestin+, and SOX1+KI67+ cells. Moreover, animals treated with exosomes exhibited a significative higher neurogenesis, as indicated by the higher percentage of DCX+MAP 2+ neurons. In vitro, hpMSC-derived exosomes promoted the proliferation of NSCs and the increase of the phosphorylated levels of MEK, ERK, and CREB. Conclusions This study provides evidence that the use of hpMSC-derived exosomes may constitute a promising therapeutic strategy for the treatment of SCI.

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“…For the use of mesenchymal stem cell exosomes, we used exosomes extracted from untreated simple cells. In the current study, some experimenters also used exosomes obtained after intervention with other substances, such as interferon gamma [47][48][49]. As with other related secretionpromoting substances, whether the use of activated exosomes is more bene cial to the treatment of diseases remains to be veri ed.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cell-derived exosomes inhibit Aβ1-42 induced microglia polarization by TLR2/MYD88/NF-κB pathway

Yin¹,

Guo²,

Wang³

et al. 2021

Preprint

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Background In recent years, more and more research evidence indicates that the causes of various neurodegeneration diseases are related to neuroinflammation in the brain, Aβ1–42 may be a key factor in the development of neuroinflammation in neurodegenerative diseases. Therefore, it is urgent to find an effective and targeted alleviation of neuroinflammation caused by Aβ1–42. Methods Our study found that exogenous administration of Aβ1–42 has a very obvious polarizing effect on microglia in the brain compared with the PBS-treated group. After the intervention of Aβ1–42, we obtained the mesenchymal stem cells derived exosome by ultracentrifugation. Microglia were treated with MSC-Exo in vivo and in vitro. Results The MSC-Exo were found have the effect of inhibiting microglial polarization in vivo and in vitro experiments. It was further found that its target gene was TLR2 on the surface of microglial cells to inhibit the expression of the downstream protein MYD88/NF-κB and inhibit the microglia polarization and the development of neuroinflammation. Conclusion MSC-Exo can significantly inhibited the Aβ1–42 induced microglia polarization by TLR2/MYD88/NF-κb pathway.

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Mesenchymal stem cell-derived exosome: a promising alternative in the therapy of Alzheimer’s disease

Cited by 114 publications

References 162 publications

Exosomes derived from miR-26a-modified MSCs promote axonal regeneration via the PTEN/AKT/mTOR pathway following spinal cord injury

Exosomes derived from miR-26a-modified MSCs promote axonal regeneration via the PTEN/AKT/mTOR pathway following spinal cord injury

Exosomes derived from human placental mesenchymal stem cells enhanced the recovery of spinal cord injury by activating endogenous neurogenesis

Mesenchymal stem cell-derived exosomes inhibit Aβ1-42 induced microglia polarization by TLR2/MYD88/NF-κB pathway

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