Three-dimensional dynamic culture and hypoxic preconditioning synergistically enhance the therapeutic effects of GMSCs on intracerebral hemorrhage DOI Creative Commons
Zhengtao Yu, Ying Xia,

Yaxuan He

et al.

Materials Today Nano, Journal Year: 2024, Volume and Issue: 26, P. 100483 - 100483

Published: May 21, 2024

Intracerebral hemorrhage (ICH) is a common cerebrovascular disorder. There still high risk of severe neurological deficits even when patients survive ICH. The application new treatment techniques can reduce mortality, but reversing damage caused by ICH remains challenging. Although cell-based therapies have shown promise in treating cerebral hemorrhage, recurring challenges are premature apoptosis transplanted cells accompanied insufficient numbers and lack engraftment the target tissue, thus limiting therapeutic efficacy. Here, we show that hypoxic preconditioning combined with three-dimensional (3D) dynamically cultured gingival lamina propria-derived MSCs (GMSCs) significantly improves cell viability, anti-apoptosis ability, efficacy compared traditional monolayers. Hypoxia-preconditioned 3D-GMSCs also exhibit notable neuroprotective promote extracellular vesicles (EVs) biogenesis potential as evidenced transwell vitro intervention experiments RNA-seq; further confirmed characterization analysis EVs. Furthermore, 3D-GMSCs-EVs derived from not only had better tissue uptake capabilities reduced bleeding mice improved motor function. Subsequent on found hypoxia-preconditioned promoted reduction neuronal oxidative stress levels mitochondrial function recovery. This study innovated culture method GMSCs, demonstrated effective modification EVs, provided ideas for establishing cell-free hemorrhage.

Language: Английский

Extracellular vesicles derived from hypoxia-preconditioned olfactory mucosa mesenchymal stem cells enhance angiogenesis via miR-612 DOI Creative Commons

Lite Ge,

Chengfeng Xun,

Wenshui Li

et al.

Journal of Nanobiotechnology, Journal Year: 2021, Volume and Issue: 19(1)

Published: Nov. 21, 2021

Mesenchymal stem cells (MSCs) play important roles in tissue repair and regeneration, such as the induction of angiogenesis, particularly under hypoxic conditions. However, molecular mechanisms underlying MSC activation remain largely unknown. MSC-derived extracellular vesicles (EVs) are vital mediators cell-to-cell communication can be directly utilized therapeutic agents for regeneration. Here, we explored effects EVs from human olfactory mucosa MSCs (OM-MSCs) on angiogenesis its mechanism. were isolated normoxic (N) OM-MSCs (N-EVs) (H) (H-EVs) using differential centrifugation identified by transmission electron microscopy flow cytometry. In vitro vivo, both types OM-MSC-EVs promoted proliferation, migration, angiogenic activities brain microvascular endothelial (HBMECs). addition, angiogenesis-stimulatory activity H-EV group was significantly enhanced compared to N-EV group. MicroRNA profiling revealed a higher abundance miR-612 H-EVs than N-EVs, while inactivation abolished treatment benefit. To explore miR-612, overexpression knock-down experiments performed mimic inhibitor or agomir antagomir miR-612. The target genes confirmed luciferase reporter assay. Gain- loss-of-function studies allowed validation (enriched OM-MSC-EVs) functional messenger that stimulates represses expression TP53 targeting 3'-untranslated region. Further assays showed promote paracrine Hypoxia-inducible factor 1-alpha (HIF-1α)-Vascular growth (VEGF) signaling HBMECs via exosomal miR-612-TP53-HIF-1α-VEGF axis. These findings suggest may represent promising strategy ischemic disease promoting transfer.

Language: Английский

Citations

96
Oxidative Stress, Inflammation, and Autophagy: Potential Targets of Mesenchymal Stem Cells-Based Therapies in Ischemic Stroke DOI Creative Commons
Jialin He, Jianyang Liu, Yan Huang

et al.

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Feb. 26, 2021

Ischemic stroke is a leading cause of death worldwide; currently available treatment approaches for ischemic are to restore blood flow, which reduce disability but time limited. The interruption flow in contributes intricate pathophysiological processes. Oxidative stress and inflammatory activity two early events the cascade cerebral injury. These factors reciprocal causation directly trigger development autophagy. Appropriate autophagy brain recovery by reducing oxidative activity, while dysfunction aggravates Abundant evidence demonstrates beneficial impact mesenchymal stem cells (MSCs) secretome on MSCs through suppressing reactive oxygen species (ROS) nitrogen (RNS) generation transferring healthy mitochondria damaged cells. Meanwhile, exert anti-inflammation properties production cytokines extracellular vesicles, inhibiting proinflammatory activation, pyroptosis, alleviating blood–brain barrier leakage. Additionally, regulation imbalances gives rise neuroprotection against Altogether, have been promising candidate due their pleiotropic effect.

Language: Английский

Citations

79
Hypoxic preconditioning rejuvenates mesenchymal stem cells and enhances neuroprotection following intracerebral hemorrhage via the miR-326-mediated autophagy DOI Creative Commons
Jianyang Liu, Jialin He,

Lite Ge

et al.

Stem Cell Research & Therapy, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 22, 2021

Abstract Background Intracerebral hemorrhage (ICH) is a major public health concern, and mesenchymal stem cells (MSCs) hold great potential for treating ICH. However, the quantity quality of MSCs decline in cerebral niche, limiting efficacy MSCs. Hypoxic preconditioning suggested to enhance survival augment therapeutic MicroRNAs (miRNAs) are known mediate cellular senescence. precise mechanism by which miRNAs regulate senescence hypoxic remains be further studied. In present study, we evaluated whether enhances effects olfactory mucosa MSC (OM-MSC) ICH investigated mechanisms miRNA ameliorates OM-MSC Methods vivo model, was induced mice administration collagenase IV. At 24 h post-ICH, 5 × 10 normoxia or hypoxia OM-MSCs saline administered intracerebrally. The behavioral outcome, neuronal apoptosis, were evaluated. vitro exposed hemin. Cellular examined evaluating expressions P16INK4A, P21, P53, β-galactosidase staining. Microarray bioinformatic analyses performed investigate differences expression profiles between OM-MSCs. Autophagy confirmed using protein levels LC3, P62, Beclin-1. Results transplanted with exhibited increased tissue-protective capability. decreased Bioinformatic analysis identified that microRNA-326 (miR-326) significantly compared Upregulation miR-326 alleviated senescence, whereas downregulation Furthermore, showed upregulating autophagy. Mechanistically, promoted autophagy via PI3K signaling pathway targeting polypyrimidine tract-binding 1 (PTBP1). Conclusions Our study shows delays augments miR-326/PTBP1/PI3K-mediated

Language: Английский

Citations

64
Artemisinin attenuated ischemic stroke induced pyroptosis by inhibiting ROS/TXNIP/NLRP3/Caspase-1 signaling pathway DOI Creative Commons
Yue Wang, Huiling Yuan,

Da Shen

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 116894 - 116894

Published: June 15, 2024

To explore the neuroprotective mechanism of artemisinin against ischemic stroke from perspective NLRP3-mediated pyroptosis.

Language: Английский

Citations

13
UBIAD1 alleviates ferroptotic neuronal death by enhancing antioxidative capacity by cooperatively restoring impaired mitochondria and Golgi apparatus upon cerebral ischemic/reperfusion insult DOI Creative Commons
Yan Huang, Jianyang Liu, Jialin He

et al.

Cell & Bioscience, Journal Year: 2022, Volume and Issue: 12(1)

Published: April 4, 2022

Neuronal death due to over-oxidative stress responses defines the pathology of cerebral ischemic/reperfusion (I/R) insult. Ferroptosis is a form oxidative cell that induced by disruption balance between antioxidants and pro-oxidants in cells. However, potential mechanisms responsible for I/R-induced ferroptotic neuronal have not been conclusively determined. UBIAD1, newly identified antioxidant enzyme catalyzes coenzyme Q10 (CoQ10) vitamin K2 biosynthesis Golgi apparatus membrane mitochondria, respectively. Even though UBIAD1 significant mediator apoptosis I/R challenge, its roles remain undefined. Therefore, we investigated whether involved injury. Further, evaluated functions possible death, with major focus on mitochondrial dysfunctions.Ferroptosis occurred I/R. Ferroptotic promoted brain tissue injury impairment. was expressed tissues localized neurons, astrocytes, microglia. Under conditions overexpressed significantly suppressed lipid peroxidation ferroptosis. Moreover, upregulated protected against damage alleviating I/R-mediated knockdown reversed these changes. Enhanced UBIAD1-mediated ferroptosis elevated antioxidative capacity rescuing dysfunction They improved morphology biofunctions mitochondria apparatus, thereby elevating levels SOD, T-AOC production CoQ10, endothelial nitric oxide synthase (eNOS)-regulated (NO) generation as well MDA generation.The neuroprotective agent, modulates restoring damaged enhancing capacities. rescue impaired mechanism regulating treatment strategy ischemic stroke.

Language: Английский

Citations

38
Paracrine Effects of Mesenchymal Stem Cells in Ischemic Stroke: Opportunities and Challenges DOI
Afsaneh Asgari Taei, Pariya Khodabakhsh, Sanaz Nasoohi

et al.

Molecular Neurobiology, Journal Year: 2022, Volume and Issue: 59(10), P. 6281 - 6306

Published: Aug. 3, 2022

Language: Английский

Citations

30
Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review) DOI Creative Commons
Xiaolu Zhang, Wenyun Zeng, Yue Zhang

et al.

International Journal of Molecular Medicine, Journal Year: 2022, Volume and Issue: 49(6)

Published: April 7, 2022

Post‑ischemic neuroinflammation induced by the innate local immune response is a major pathophysiological feature of cerebral ischemic stroke, which remains leading cause mortality and disability worldwide. NLR family pyrin domain containing (NLRP)3 inflammasome crucially mediates post‑ischemic inflammatory responses via its priming, activation interleukin‑1β release during hypoxic‑ischemic brain damage. Mitochondrial dysfunctions are among main hallmarks several diseases, including stroke. In present review, focus was addressed on role mitochondria in stroke while keeping NLRP3 as link. Under ischemia hypoxia, capable controlling inflammasome‑mediated through mitochondrial released contents, localization related proteins. Thus, may be attractive targets to treat well drugs that target process function At present, certain have already been studied clinical trials.

Language: Английский

Citations

27
Mesenchymal Stem Cell Therapy: A Potential Treatment Targeting Pathological Manifestations of Traumatic Brain Injury DOI Creative Commons
Kaige Zhang, Yiming Jiang, Biyao Wang

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 11

Published: June 15, 2022

Traumatic brain injury (TBI) makes up a large proportion of acute injuries and is major cause disability globally. Its complicated etiology pathogenesis mainly include primary secondary over time, which can cognitive deficits, physical disabilities, mood changes, impaired verbal communication. Recently, mesenchymal stromal cell- (MSC-) based therapy has shown significant therapeutic potential to target TBI-induced pathological processes, such as oxidative stress, neuroinflammation, apoptosis, mitochondrial dysfunction. In this review, we discuss the main processes TBI summarize underlying mechanisms MSC-based treatment. We also research progress in field MSC well shortcomings great shown.

Language: Английский

Citations

21
SENP1 facilitates OM-MSC differentiation through activating OPTN-mediated mitophagy to mitigate the neurologic impairment following ICH DOI Creative Commons
Jun He, Jun Peng,

You Li

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109865 - 109865

Published: April 30, 2024

Previous studies have indicated the neuroprotective effect of olfactory mucosa mesenchymal stem cells (OM-MSCs) on brain injury. Intracerebral hemorrhage (ICH) models were established in rats by injecting autologous blood. SENP1 expression was enhanced neurons but decreased astrocytes compared to that OM-MSCs. Overexpression promoted proliferation and neuronal differentiation, while inhibiting astrocytic differentiation Conversely, its knockdown had opposite effect. Moreover, OM-MSCs reduced neurological dysfunction after ICH, could be further overexpression. In addition, mitophagy, which might related SENP1-mediated OPTN deSUMOylation. Furthermore, through mitophagy mediated OPTN. Similar SENP1, transfection remission OM-MSC ICH rats. OPTN-mediated improve deficits

Language: Английский

Citations

4
Hypoxia-preconditioned mesenchymal stem cells attenuate microglial pyroptosis after intracerebral hemorrhage DOI Open Access
Jianyang Liu, Jialin He, Yan Huang

et al.

Annals of Translational Medicine, Journal Year: 2021, Volume and Issue: 9(17), P. 1362 - 1362

Published: Sept. 1, 2021

Microglia plays a vital role in neuroinflammation, contributing to the pathogenesis of intracerebral hemorrhage (ICH)-induced brain injury. Mesenchymal stem cells (MSCs) hold great potential for treating ICH. We previously revealed that MSCs ameliorate microglial pyroptosis caused by an ischemic stroke. However, whether can modulate after ICH remains unknown. This study aimed investigate neuroprotective effects hypoxia-preconditioned olfactory mucosa (OM-MSCs) on and possible mechanisms.ICH was induced mice via administration collagenase IV. At 6 h post-ICH, 2-4×105 normoxic/hypoxic OM-MSCs or saline were intracerebrally administered. To evaluate effects, behavioral outcome, apoptosis, neuronal injury measured. activation pro-inflammatory cytokines applied detect neuroinflammation. Microglial determined western blotting, immunofluorescence staining, transmission electron microscopy (TEM).The two OM-MSC-transplanted groups exhibited significantly improved functional recovery reduced injury, especially hypoxic group. Hypoxic attenuated as well levels interleukin-1β (IL-1β) tumor necrosis factor-α (TNF-α). Moreover, we found ameliorated diminishing pyroptosis-associated proteins peri-hematoma tissues, decreasing expression nod-like receptor family protein 3 (NLRP3) caspase-1, reducing membrane pores microglia post-ICH.Our showed preconditioning augments therapeutic efficacy OM-MSCs, alleviate model.

Language: Английский

Citations

27