Bone marrow mesenchymal stem cells-derived exosomes improve injury of hippocampal neurons in rats with depression by upregulating microRNA-26a expression

Guo, Huimin; Huang, Bai-Ling; Wang, Yali; Zhang, Yanyan; Ma, Quangang; Ren, Yuming

doi:10.1016/j.intimp.2020.106285

Cited by 39 publications

(21 citation statements)

References 40 publications

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“…Along the same line, Guo et al. [ 50 ] found that the MSC-Exo elevated superoxide dismutase (SOD) levels and lowered the malondialdehyde (MDA), Lactate dehydrogenase (LDH), TNFα, and interleukin-1β (IL-1β) levels in the hippocampal neurons of rats with depression by upregulating the microRNA-26a expression.…”

Section: Discussionmentioning

confidence: 95%

Stem cell-derived exosomes and copper sulfide nanoparticles attenuate the progression of neurodegenerative disorders induced by cadmium in rats

Zaazaa

El-Motelp

Ali

et al. 2022

Heliyon

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The goal of the current study was to investigate the therapeutic effects of exosomes derived from mesenchymal stem cells (MSCs-Exo) and copper sulfide nanoparticles (CuSNPs) as biomaterials in order to understand the mechanisms that contribute to overcoming cadmium (Cad) induced neurological disorders in rats. Animals were divided into five groups (n = 10): group 1 was served as a negative control and receive vehicle saline (Con), group 2 Positive control groups were received Cad as cadmium chloride at a dose of 20 mg/kg/day for six weeks (Cad group), group 3 was received Cad plus MSCs-Exo as a single dose of 100 μLi. v. (Cad + MSCs-Exo), group 4 was received Cad plus CuSNPs at a dose of 6.5 mg/kg orally (Cad + CuSNPs), group 5 was received Cad + MSCs-Exo + CuSNPs for six weeks. However, the activities of each acetylcholine (Ach), acetylcholinesterase (AchE), total antioxidant status (TAC) were measured. Also, the levels of ROS, nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), Brain brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were evaluated. Beneficial effects on the behavior of animals were observed after treatment with MSCs-Exo and CuSNPs. Furthermore, the administration of MSCs-Exo and CuSNPs have been improve the TAC, BDNF and NGF via ameliorating the oxidative stress and inflammatory markers. Moreover, Histopathological studies had shown that great development in the brain of Cad rats treated with MSCs-Exo and CuSNPs. In conclusion, this study offers an overview of innovative stem cell therapy techniques and how to integrate them with nanotechnology to boost therapeutic performance.

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Section: Discussionmentioning

confidence: 95%

Stem cell-derived exosomes and copper sulfide nanoparticles attenuate the progression of neurodegenerative disorders induced by cadmium in rats

Zaazaa

El-Motelp

Ali

et al. 2022

Heliyon

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“…Many studies have demonstrated that exosomal miRNAs can play important roles in treatment or detected markers of many diseases, including cancer progression and metastasis [42,43], neurodegenerative diseases [44][45][46], and inflammation [47], and they also participate in the pathological of depression [48,49]. Furthermore, mesenchymal stem cell-derived exosomal miR26a can improve symptoms of depression in rats [50]. Next, by microarray and bioinformatics analysis, we confirmed that miR-207 had a higher expression in exosomes from unstressed mice compared with those from stressed mice and could be an important role in the treatment of stress mice.…”

Section: Discussionmentioning

confidence: 99%

NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice

Wang

Jin

et al. 2020

J Neuroinflammation

103

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Background: Depression is a common mental disease that mainly manifests as bad mood, decreased interest, pessimism, slow thinking, lack of initiative, poor diet and sleep. Patients with severe depression have suicidal tendencies. Exosomes are small vesicles released by the fusion of a multivesicular body and membranes, and they contain specific proteins, nucleic acids, and lipids related to the cells from which they originate. MicroRNAs (miRNAs) are 20-24 nt RNAs that can be packaged into exosomes and can play important regulatory roles. Astrocytes are the most abundant cell population in the central nervous system and have a close link to depression. Astrocyte activation could result in the release of inflammatory cytokines, including IL-1β, IL-6, and TNFα, which could promote the symptoms of depression. In previous research, our team confirmed that NK cells regulate depression in mice. Here, we propose that miRNA in the exosomes from NK cells performs this antidepressant function.Methods: Exosomes from NK cells were shown by in vivo and in vitro experiments to alleviate symptoms of chronic mild stress in mice and decrease pro-inflammatory cytokines release from astrocytes. The production of pro-inflammatory cytokines was assessed by ELISA. Microarray analysis was used to identify critical miRNAs. Luciferase reporter assays, qPCR, and other experiments were used to prove that exosomal miR-207 has an important role in alleviating the symptoms of stress in mice.Results: MiRNA-containing exosomes from NK cells could alleviate symptoms of chronic mild stress in mice. In vivo experiments showed that these exosomes decreased the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNFα) released by astrocytes. By microarray analysis of exosome miRNA profiles, miR-207 was found to be overexpressed in exosomes derived from unstressed mice. Experiments confirmed that miR-207 directly targets TLR4 interactor with leucine-rich repeats (Tril) and inhibits NF-κB signaling in astrocytes. MiR-207 could decrease the release of pro-inflammatory cytokines and inhibit expression of Tril in vitro. In vivo experiments revealed that exosomes with low miR-207 levels showed decreased antidepressant activity.(Continued on next page) Conclusion: Collectively, our findings revealed that exosomal miR-207 alleviated symptoms of depression in stressed mice by targeting Tril to inhibit NF-κB signaling in astrocytes.

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“…IL6, IL8, IL1β, TNFα, IFNα) that can further exacerbate the inflammatory response [60,114]. In recent years, the neuroprotective and anti-inflammatory properties of stem cell EVs have been well-documented; in the context of the CNS, there is accumulating evidence that stem cell EVs may be able to reverse neuronal apoptosis and modulate the polarization of both astrocytes and microglia from pro-inflammatory to anti-inflammatory phenotypes [81,82,83,84,85,86,87,88,89,90,91,92]. To the best of our knowledge, the functional effects of stem cell EVs on 3D cultures has not previously been reported.…”

Section: Discussionmentioning

confidence: 99%

“…After confirming EV uptake by neurospheres we shifted our focus to next examine their potential functional effects in HIV-1 infected neurospheres. To date, the anti-apoptotic effects of stem cell EVs in the context of the CNS have been well documented both in vitro and in vivo [81,82,83,84,85,86]. To this end, we performed western blot to examine the expression levels of different proteins involved in the regulation of apoptosis ( Fig.…”

Section: The Effect Of Stem Cell Evs On Hiv-1 Infected Neurospheresmentioning

confidence: 99%

Retroviral Infection of Human Neurospheres and Use of Stem Cell EVs to Repair Cellular Damage

Branscome

Yin²,

Jacob³

et al. 2021

Preprint

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HIV-1 remains an incurable infection that is associated with substantial economic and epidemiologic impacts. HIV-associated neurocognitive disorders (HAND) are commonly linked with HIV-1 infection; despite the development of combination antiretroviral therapy (cART), HAND is still reported to affect at least 50% of HIV-1 infected individuals. It is believed that the over-amplification of inflammatory pathways, along with release of toxic viral proteins from infected cells, are primarily responsible for the neurological damage that is observed in HAND; however, the underlying mechanisms are not well-defined. Therefore, there is an unmet need to develop more physiologically relevant and reliable platforms for studying these pathologies. In recent years, neurospheres derived from induced pluripotent stem cells (iPSCs) have been utilized to model the effects of different neurotropic viruses. Here, we report the generation of neurospheres from iPSC-derived neural progenitor cells (NPCs). We show, for what we believed to be the first time, that these cultures are susceptible to retroviral (e.g. HIV-1, HTLV-1) infection. In addition, we also examine the functional effects of stem cell derived extracellular vesicles (EVs) on HIV-1 damaged cells as there is abundant literature supporting the reparative and regenerative properties of stem cell EVs in the context of various CNS pathologies. Consistent with the literature, our data suggests that stem cell EVs may modulate neuroprotective and anti-inflammatory properties in damaged cells. Collectively, this study demonstrates the feasibility of NPC-derived neurospheres for modeling HIV-1 infection and, subsequently, highlights the potential of stem cell EVs for rescuing cellular damage induced by HIV-1 infection.

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Bone marrow mesenchymal stem cells-derived exosomes improve injury of hippocampal neurons in rats with depression by upregulating microRNA-26a expression

Cited by 39 publications

References 40 publications

Stem cell-derived exosomes and copper sulfide nanoparticles attenuate the progression of neurodegenerative disorders induced by cadmium in rats

Stem cell-derived exosomes and copper sulfide nanoparticles attenuate the progression of neurodegenerative disorders induced by cadmium in rats

NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice

Retroviral Infection of Human Neurospheres and Use of Stem Cell EVs to Repair Cellular Damage

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