Mesenchymal Stem Cell-Derived Extracellular Vesicles Ameliorates Hippocampal Synaptic Impairment after Transient Global Ischemia

Deng, Mingyang; Xiao, Han; Zhang, Hainan; Peng, Hongling; Yuan, Huan; Xu, Yadong; Zhang, Guangsen; Hu, Zhiping

doi:10.3389/fncel.2017.00205

Cited by 56 publications

(41 citation statements)

References 33 publications

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“…BMSCs have been widely investigated because of their therapeutic potential in various diseases such as nervous system diseases and autoimmune diseases (13,(30)(31)(32)(33). Recently, the use of BMSCs in renal I/R injury therapies has generated interest; nevertheless, the therapeutic features and underlying mechanisms remain elusive and need to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported that the therapeutic effects of BMSCs were a result of their differentiation potential; however, reports have increasingly suggested that the functions of BMSCs might be attributable to potent paracrine activities such as cytoprotective factors and exosomes (15,32,35,36). A series of cytoprotective factors secreted by BMSCs have been demonstrated to play the important mediatory function of BMSCs (37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

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BMSCs protect against renal ischemia‐reperfusion injury by secreting exosomes loaded with miR‐199a‐5p that target BIP to inhibit endoplasmic reticulum stress at the very early reperfusion stages

Wang

Zhu

et al. 2019

FASEB j.

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Bone marrow–derived mesenchymal stem cells (BMSCs) have been recently reported to play a variety of vital roles in organ and tissue damage repair, mainly via potent paracrine activity, including secreting extracellular vesicles, such as exosomes, that serve as mediators facilitating intercellular communication and reprogramming recipient cells by delivering their contents to target cells. However, the underlying mechanisms are diverse and complex, and the influencing characteristics have rarely been studied. Accordingly, we designed this study to explore the time dependence of the effects of exosomes derived from BMSCs (BMexos) on renal ischemia‐reperfusion (I/R) injury and the underlying mechanisms associated with the reperfusion time. Impressively, our study is the first to find that BMexos protected against renal I/R injury in vitro and in vivo at the very early reperfusion stages, especially 4–8 h after reperfusion in vitro and 8–16 h after reperfusion in vivo. Interestingly, we simultaneously found that endoplasmic reticulum (ER) stress was significantly suppressed following the administration of BMexos in vitro and in vivo with a similar time dependence. Additionally, we discovered that miR‐199a‐5p, which was abundant in the BMSCs, was transferred into renal tubular epithelial cells (NRK‐52E) in a time‐dependent manner and significantly inhibited I/R‐induced ER stress by targeting binding immunoglobulin protein (BIP). Cocultivation with miR‐199a‐5p‐overexpressing BMSCs amplified the suppression of ER stress and further protected against I/R injury. However, coculture with miR‐199a‐5p‐knockdown BMSCs obviously increased ER stress and reversed the BMexos‐induced protection, and silencing BIP by small interfering RNA–1098 in NRK‐52E inhibited these effects. This study provides evidence that administering BMexos at the very early reperfusion stages significantly protects against renal I/R injury, and ER stress is closely linked to this protection. These results suggest a novel therapeutic strategy during the very early reperfusion stages of renal I/R injury.—Wang, C., Zhu, G., He, W., Yin, H., Lin, F., Gou, X., Li, X. BMSCs protect against renal ischemia‐reperfusion injury by secreting exosomes loaded with miR‐199a‐5p that target BIP to inhibit endoplasmic reticulum stress at the very early reperfusion stages. FASEB J. 33, 5440–5456 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

BMSCs protect against renal ischemia‐reperfusion injury by secreting exosomes loaded with miR‐199a‐5p that target BIP to inhibit endoplasmic reticulum stress at the very early reperfusion stages

Wang

Zhu

et al. 2019

FASEB j.

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“…Since MSC-derived EVs are also able to ameliorate hippocampal synaptic impairment after ischemia [303] as well as memory dysfunction after status epilepticus [304], these vesicles are at the moment the object of much research aimed at finding out new therapies for brain injury and malfunction.…”

Section: Natural As Well As Engineered Evs As Drug Carriersmentioning

confidence: 99%

Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles

Schiera

Liegro

2019

IJMS

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Most aspects of nervous system development and function rely on the continuous crosstalk between neurons and the variegated universe of non-neuronal cells surrounding them. The most extraordinary property of this cellular community is its ability to undergo adaptive modifications in response to environmental cues originating from inside or outside the body. Such ability, known as neuronal plasticity, allows long-lasting modifications of the strength, composition and efficacy of the connections between neurons, which constitutes the biochemical base for learning and memory. Nerve cells communicate with each other through both wiring (synaptic) and volume transmission of signals. It is by now clear that glial cells, and in particular astrocytes, also play critical roles in both modes by releasing different kinds of molecules (e.g., D-serine secreted by astrocytes). On the other hand, neurons produce factors that can regulate the activity of glial cells, including their ability to release regulatory molecules. In the last fifteen years it has been demonstrated that both neurons and glial cells release extracellular vesicles (EVs) of different kinds, both in physiologic and pathological conditions. Here we discuss the possible involvement of EVs in the events underlying learning and memory, in both physiologic and pathological conditions.

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“…MSC-EVs have also been reported to reduce the hepatic injury by improving the hepatocytes viability, suppressing oxidative injury and modulating the inflammatory response in vivo [10]. MSCs-derived EVs were also successfully applied to treat transient global ischemia in mice, where the neuroprotective effects of MSC-EVs were demonstrated [11]. Based on these findings, the cell-free therapy concept was developed, where the MSCs-derived EVs are used instead of cells [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells

Gomzikova

Zhuravleva

Vorobev

et al. 2019

Cells

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The cytochalasin B-induced membrane vesicles (CIMVs) are suggested to be used as a vehicle for the delivery of therapeutics. However, the angiogenic activity and therapeutic potential of human mesenchymal stem/stromal cells (MSCs) derived CIMVs (CIMVs-MSCs) remains unknown. Objectives: The objectives of this study were to analyze the morphology, size distribution, molecular composition, and angiogenic properties of CIMVs-MSCs. Methods: The morphology of CIMVs-MSC was analyzed by scanning electron microscopy. The proteomic analysis, multiplex analysis, and immunostaining were used to characterize the molecular composition of the CIMVs-MSCs. The transfer of surface proteins from a donor to a recipient cell mediated by CIMVs-MSCs was demonstrated using immunostaining and confocal microscopy. The angiogenic potential of CIMVs-MSCs was evaluated using an in vivo approach of subcutaneous implantation of CIMVs-MSCs in mixture with Matrigel matrix. Results: Human CIMVs-MSCs retain parental MSCs content, such as growth factors, cytokines, and chemokines: EGF, FGF-2, Eotaxin, TGF-α, G-CSF, Flt-3L, GM-CSF, Fractalkine, IFNα2, IFN-γ, GRO, IL-10, MCP-3, IL-12p40, MDC, IL-12p70, IL-15, sCD40L, IL-17A, IL-1RA, IL-1a, IL-9, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IP-10, MCP-1, MIP_1a, MIP-1b, TNF-α, TNF-β, VEGF. CIMVs-MSCs also have the expression of surface receptors similar to those in parental human MSCs (CD90+, CD29+, CD44+, CD73+). Additionally, CIMVs-MSCs could transfer membrane receptors to the surfaces of target cells in vitro. Finally, CIMVs-MSCs can induce angiogenesis in vivo after subcutaneous injection into adult rats. Conclusions: Human CIMVs-MSCs have similar content, immunophenotype, and angiogenic activity to those of the parental MSCs. Therefore, we believe that human CIMVs-MSCs could be used for cell free therapy of degenerative diseases.

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Mesenchymal Stem Cell-Derived Extracellular Vesicles Ameliorates Hippocampal Synaptic Impairment after Transient Global Ischemia

Cited by 56 publications

References 33 publications

BMSCs protect against renal ischemia‐reperfusion injury by secreting exosomes loaded with miR‐199a‐5p that target BIP to inhibit endoplasmic reticulum stress at the very early reperfusion stages

BMSCs protect against renal ischemia‐reperfusion injury by secreting exosomes loaded with miR‐199a‐5p that target BIP to inhibit endoplasmic reticulum stress at the very early reperfusion stages

Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles

Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells

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