Mesenchymal stem cell-derived extracellular vesicles attenuate tPA-induced blood–brain barrier disruption in murine ischemic stroke models

Qiu, Lina; Cheng, Ying; Geng, Yanqin; Yao, Xiuhua; Wang, Lanxing; Cao, Hongmei; Zhang, Xuebin; Wu, Qiaoli; Kong, Deling; Shi, Yang; Wang, Yuebing; Wu, Jialing

doi:10.1016/j.actbio.2022.10.022

Cited by 31 publications

(25 citation statements)

References 78 publications

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“…Our study provides new evidence for the association of microRNAs with PH in AIS after mechanical reperfusion therapy. Most differentially expressed microRNAs were not reported to be involved in PH after reperfusion [20,21,[36][37][38][39][40][41].…”

Section: Discussionmentioning

confidence: 99%

“…Twelve genes were associated with all the oxidative stress, apoptosis, immune, and inflammation. Twelve genes had been reported as a potential regulator for HT in ischemic stroke in previous studies, including CASP3, CSF2, CTNNB1, CXCL12, HIF1A, IL1B, MTOR, PTGS2, PTPRC, TLR2, TLR4, VCAM1 [38,39,[46][47][48][49][50][51][52][53][54][55]. The other 19 genes may be a potential therapy target for improving PH in acute ischemic stroke after mechanical reperfusion treatment.…”

Section: Discussionmentioning

confidence: 99%

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MicroRNAs and mRNA Regulatory Network of Parenchymal Hematoma after Endovascular Mechanical Reperfusion for Acute Ischemic Stroke in Rat

Zhuang,

Huang,

Qin

et al. 2024

Preprint

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Hemorrhagic transformation after endovascular thrombectomy predicts poor outcomes in acute ischemic stroke with large vessel occlusion. The roles of microRNAs in the pathogenesis of parenchymal hematoma (PH) are still unclear. This study aims to investigate the microRNA and mRNA regulatory network associated with PH after mechanical reperfusion in the animal stroke model and oxygen-glucose deprivation/reoxygenation (OGD/R) model. Twenty-five microRNAs were assessed in the reperfusion-induced hemorrhage model in rats with hyperglycemic conditions receiving 5-hour middle cerebral artery occlusion. Thirteen down-regulated microRNAs (miRNA-29a-5p, miRNA-29c-3p, miRNA-126a-5p, miRNA-132-3p, miRNA-136-3p, miRNA-142-3p, miRNA-153-5p, miRNA-218a-5p, miRNA-219a-2-3p, miRNA-369-5p, miRNA-376a-5p, miRNA-376b-5p, miRNA-383-5p) and one up-regulated microRNA (miRNA-195-3p) were found in rat peri-infarct with PH. Ten of these 14 PH-related microRNAs were significantly differentially expressed in at least two of five models of neuron, astrocyte, microglia, BMEC, and pericyte after OGD/R, consistent with the animal model results. Thirty-one predicted hub target genes were significantly differentially expressed in rat peri-infarct with PH. Forty-nine microRNA-mRNA regulatory axes of PH were revealed, which were related to the mechanisms of oxidative stress, apoptosis, immune, and inflammation. Simultaneously differentially expressed microRNAs and related genes in several cells of the neurovascular unit may serve as valuable targets for PH after endovascular thrombectomy in acute ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MicroRNAs and mRNA Regulatory Network of Parenchymal Hematoma after Endovascular Mechanical Reperfusion for Acute Ischemic Stroke in Rat

Zhuang,

Huang,

Qin

et al. 2024

Preprint

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“…To advance our understanding, additional multimodal imaging technologies are needed for studying brain cell uptake and the real-time localization of drugs. [33][34][35][36] (3) In-depth investigation of interactions between nanodelivery systems, drug formulation, and neural pathways: The precise mechanism by which drugs enter the brain through INA delivery systems remains unclear. Combining in-silico modeling of the intranasal environment with experimental studies on drug-nanocarrier interactions and their interactions with cells can provide valuable insights for the rational design of drug delivery systems.…”

Section: Discussionmentioning

confidence: 99%

“…(2) Multimodal real‐time tracing system for precise assessment of INA delivery efficiency: Currently, the quantification of INA delivery efficiency primarily relies on mathematical modeling and tomographic slices. To advance our understanding, additional multimodal imaging technologies are needed for studying brain cell uptake and the real‐time localization of drugs 33–36 …”

Section: Discussionmentioning

confidence: 99%

Chances and challenges in intranasal administration delivery for brain disease treatment

Zheng,

Guo,

Yan

et al. 2023

Clinical and Translational Dis

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In order to overcome the formidable challenges posed by the intricate physiological barriers of the brain, the employment of intranasal administration (INA) has emerged as an unconventional method for drug delivery, offering distinct advantages such as non‐invasiveness and enhanced pharmacokinetic characteristics within the brain. Primarily exploiting the distinct conduit offered by the olfactory and/or trigeminal nerve systems, the INA route effectively delivers therapeutic agents. With introducing appropriate improvements to the drug formulation, such as the incorporation of nanocarriers, the efficacious delivery via the INA approach has gained considerable traction for the treatment of neurological disorders. This concise review highlights the notable progress in INA delivery and explores the potential therapeutic modalities inherent in this promising paradigm.

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“…The first‐ever siRNA interference‐based therapy approved by the FDA for hereditary transthyretin amyloidosis was encapsulated in such membrane vesicles (Food, 2018). In this context, there is compelling evidence that these membrane‐based nanoparticles, more importantly, mesenchymal stem cell‐derived EVs (MSC‐EVs), have undergone tremendous advancements in their utility as biomarkers and therapeutics of various organ conditions such as lung injury/disease (Sharma et al., 2022, Zhao et al., 2022), liver regeneration/injury (Lu et al., 2022, Zhang et al., 2023), bone repair/bone tissue regeneration (Cha et al., 2023, Huang et al., 2023, Warmink et al., 2023), graft‐versus‐host disease (Madel et al., 2023), wound healing (Kim et al., 2023, Las Heras et al., 2022), COVID‐19 induced infection (Chutipongtanate et al., 2022), blood‐brain‐barrier disruption (BBB) (Qiu et al., 2022), and various neurodegenerative disorders (Xu et al., 2022). Studies indicate that these EVs are the primary and fundamental paracrine effectors of MSCs and can effectively replicate the therapeutic properties of MSCs (Kou et al., 2022, Tsiapalis et al., 2023).…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell‐derived extracellular vesicles: Recent therapeutics and targeted drug delivery advances

Bhat,

Malik,

Yadav

et al. 2024

J of Extracellular Bio

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The targeted drug delivery field is rapidly advancing, focusing on developing biocompatible nanoparticles that meet rigorous criteria of non‐toxicity, biocompatibility, and efficient release of encapsulated molecules. Conventional synthetic nanoparticles (SNPs) face complications such as elevated immune responses, complex synthesis methods, and toxicity, which restrict their utility in therapeutics and drug delivery. Extracellular vesicles (EVs) have emerged as promising substitutes for SNPs, leveraging their ability to cross biological barriers, biocompatibility, reduced toxicity, and natural origin. Notably, mesenchymal stem cell‐derived EVs (MSC‐EVs) have garnered much curiosity due to their potential in therapeutics and drug delivery. Studies suggest that MSC‐EVs, the central paracrine contributors of MSCs, replicate the therapeutic effects of MSCs. This review explores the characteristics of MSC‐EVs, emphasizing their potential in therapeutics and drug delivery for various diseases, including CRISPR/Cas9 delivery for gene editing. It also delves into the obstacles and challenges of MSC‐EVs in clinical applications and provides insights into strategies to overcome the limitations of biodistribution and target delivery.

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Mesenchymal stem cell-derived extracellular vesicles attenuate tPA-induced blood–brain barrier disruption in murine ischemic stroke models

Cited by 31 publications

References 78 publications

MicroRNAs and mRNA Regulatory Network of Parenchymal Hematoma after Endovascular Mechanical Reperfusion for Acute Ischemic Stroke in Rat

MicroRNAs and mRNA Regulatory Network of Parenchymal Hematoma after Endovascular Mechanical Reperfusion for Acute Ischemic Stroke in Rat

Chances and challenges in intranasal administration delivery for brain disease treatment

Mesenchymal stem cell‐derived extracellular vesicles: Recent therapeutics and targeted drug delivery advances

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