Potential Role of Exosomes in Ischemic Stroke Treatment

Biomolecules, Journal Year: 2022, Volume and Issue: 12(1), P. 115 - 115

Published: Jan. 11, 2022

Ischemic stroke is a life-threatening cerebral vascular disease and accounts for high disability mortality worldwide. Currently, no efficient therapeutic strategies are available promoting neurological recovery in clinical practice, except rehabilitation. The majority of neuroprotective drugs showed positive impact pre-clinical studies but failed trials. Therefore, there an urgent demand new promising approaches ischemic treatment. Emerging evidence suggests that exosomes mediate communication between cells both physiological pathological conditions. Exosomes have received extensive attention therapy following stroke, because their unique characteristics, such as the ability to cross blood brain–barrier, low immunogenicity, toxicity. An increasing number demonstrated positively neurorestorative effects exosome-based therapy, which largely mediated by microRNA cargo. Herein, we review current knowledge exosomes, relationships treatments neurovascular remodeling processes after stroke. provide viable prospective treatment strategy patients.

Language: Английский

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Therapeutic potential of mesenchymal stem cell-derived exosomes and miRNAs in neuronal regeneration and rejuvenation in neurological disorders: a mini review

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Oct. 4, 2024

Mesenchymal stem cells (MSCs) have gained considerable attention in the field of regenerative medicine due to their ability secrete small extracellular vesicles (EVs) known as exosomes. This review delves into various biological activities MSCs and cell interactions enabled by these exosomes, with a focus on potential for neuronal regeneration treatment neurological disorders. We scrutinize findings from multiple studies that underscore neuroprotective neuro-regenerative effects exosomes derived MSCs, illuminating mechanisms action therapeutic applications. thoroughly investigates all related pathways, miRNAs, factors suggest strategies enhancing therapy disorders using boosting regeneration.

Language: Английский

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Lithium modulates miR-1906 levels of mesenchymal stem cell-derived extracellular vesicles contributing to poststroke neuroprotection by toll-like receptor 4 regulation

Stem Cells Translational Medicine, Journal Year: 2020, Volume and Issue: 10(3), P. 357 - 373

Published: Nov. 4, 2020

Lithium is neuroprotective in preclinical stroke models. In addition to that, poststroke neuroregeneration stimulated upon transplantation of mesenchymal stem cells (MSCs). Preconditioning MSCs with lithium further enhances the neuroregenerative potential MSCs, which act by secreting extracellular vesicles (EVs). The present work analyzed whether MSC preconditioning modifies EV secretion patterns, enhancing therapeutic such derived EVs (Li-EVs) comparison enriched from native MSCs. Indeed, Li-EVs significantly enhanced resistance cultured astrocytes, microglia, and neurons against hypoxic injury when compared controls EV-treated cells. Using a mouse model, intravenous delivery increased neurological recovery for as long 3 months mice, albeit latter also showed better behavioral test performance controls. changed patterns EVs, modifying contents various miRNAs within these vesicles. As such, displayed levels miR-1906, has been shown be new regulator toll-like receptor 4 (TLR4) signaling. reduced posthypoxic postischemic TLR4 abundance, resulting an inhibition nuclear factor kappa-light-chain-enhancer activated B (NF-κB) signaling pathway, decreased proteasomal activity, declined both inducible NO synthase cyclooxygenase-2 expression, all culminated cerebral inflammation. Conclusively, study demonstrates, first time, interfering novel pathway that yields acute neuroprotection recovery.

Language: Английский

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Dysfunction of the Neurovascular Unit in Ischemic Stroke: Highlights on microRNAs and Exosomes as Potential Biomarkers and Therapy

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(11), P. 5621 - 5621

Published: May 25, 2021

Ischemic stroke is a damaging cerebral vascular disease associated with high disability and mortality rates worldwide. In spite of the continuous development new diagnostic prognostic methods, early detection outcome prediction are often very difficult. The neurovascular unit (NVU) complex multicellular entity linking interactions between neurons, glial cells, brain vessels. Novel research has revealed that exosome-mediated transfer microRNAs plays an important role in cell-to-cell communication and, thus, integral crosstalk within NVU. After stroke, NVU homeostasis altered, which induces release several potential biomarkers into blood addition biological data representing all constituents to clinical neuroradiological findings can significantly advance evaluation prognosis. this review, we present current literature regarding possible beneficial roles exosomes derived from components multipotent mesenchymal stem cells preclinical studies ischemic stroke. We also discuss most relevant trials on patients.

Language: Английский

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Role of Mesenchymal Stem Cells and Their Paracrine Mediators in Macrophage Polarization: An Approach to Reduce Inflammation in Osteoarthritis

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 13016 - 13016

Published: Oct. 27, 2022

Osteoarthritis (OA) is a low-grade inflammatory disorder of the joints that causes deterioration cartilage, bone remodeling, formation osteophytes, meniscal damage, and synovial inflammation (synovitis). The synovium primary site in OA frequently characterized by hyperplasia lining infiltration cells, primarily macrophages. Macrophages play crucial role early response through production several cytokines, chemokines, growth factors, proteinases. These pro-inflammatory mediators are activators numerous signaling pathways trigger other cytokines to further recruit more macrophages joint, ultimately leading pain disease progression. Very few therapeutic alternatives available for treating due condition's low self-healing capacity lack clear diagnostic biomarkers. In this review, we opted explore immunomodulatory properties mesenchymal stem cells (MSCs) their paracrine mediators-dependent as intervention OA, with focus on practicality polarizing suppression M1 enhancement M2 can significantly reduce symptoms.

Language: Английский

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Lithium and Copper Induce the Osteogenesis-Angiogenesis Coupling of Bone Marrow Mesenchymal Stem Cells via Crosstalk between Canonical Wnt and HIF-1α Signaling Pathways

Stem Cells International, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 15

Published: March 6, 2021

The combination of osteogenesis and angiogenesis dual-delivery trace element-carrying bioactive scaffolds stem cells is a promising method for bone regeneration repair. Canonical Wnt HIF-1α signaling pathways are vital BMSCs’ osteogenic differentiation secretion factors, respectively. Simultaneously, lithium (Li) copper (Cu) can activate the canonical pathway, Moreover, emerging evidence has shown that HIF related to coupling angiogenesis. However, it still unclear whether lithium- copper-doped scaffold induce in BMSCs underlying mechanism. So, we fabricated (Li+-) copper- (Cu2+-) doped organic/inorganic (Li 2.5-Cu 1.0-HA/Col) evaluate effects on further explore its We investigated sustained release from Li 1.0-HA/Col could couple osteogenesis- angiogenesis-related factor seeding it. our results showed 500 μM Li+ pathway rescue XAV-939 inhibition In addition, demonstrated 25 Cu2+ was similar 1% oxygen environment terms effectiveness activating pathway. More importantly, stimuli process upregulate gene expression via crosstalk between conclusion, this study revealed when they sustainably released Li-Cu-HA/Col scaffold.

Language: Английский

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Immunomodulation: The next target of mesenchymal stem cell-derived exosomes in the context of ischemic stroke

World Journal of Stem Cells, Journal Year: 2023, Volume and Issue: 15(3), P. 52 - 70

Published: March 22, 2023

Ischemic stroke (IS) is the most prevalent form of brain disease, characterized by high morbidity, disability, and mortality. However, there still a lack ideal prevention treatment measures in clinical practice. Notably, transplantation therapy mesenchymal stem cells (MSCs) has been hot research topic stroke. Nevertheless, are risks associated with this cell therapy, including tumor formation, coagulation dysfunction, vascular occlusion. Also, growing number studies suggest that therapeutic effect after MSCs mainly attributed to MSC-derived exosomes (MSC-Exos). And cell-free mediated appears circumvent many difficulties when compared it may be promising new strategy for treating as replacement therapy. Studies suppressing inflammation via modulation immune response an additional option IS. Intriguingly, MSC-Exos mediates inflammatory following IS modulating central nervous system, peripheral immunomodulatory molecules, thereby promoting neurofunctional recovery Thus, paper reviews role, potential mechanisms, post-IS order identify targets.

Language: Английский

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Microglia and Stem Cells for Ischemic Stroke Treatment—Mechanisms, Current Status, and Therapeutic Challenges

Frontiers in Bioscience-Landmark, Journal Year: 2023, Volume and Issue: 28(10)

Published: Oct. 27, 2023

Ischemic stroke is one of the major causes death and disability. Since currently used treatment option reperfusion therapy has several limitations, ongoing research focusing on neuroprotective effects microglia stem cells. By exerting bystander effect, secreting exosomes forming biobridges, mesenchymal cells (MSCs), neural (NSCs), induced pluripotent (iPSCs), multilineage-differentiating stress-enduring (Muse cells) have been shown to stimulate neurogenesis, angiogenesis, cell migration, reduce neuroinflammation. Exosome-based now being extensively researched due its many advantageous properties over therapy, such as lower immunogenicity, no risk blood vessel occlusion, ease storage modification. However, although preclinical studies promising therapeutic outcomes, clinical trials associated with translational challenges. This review explores preconditioned well various factors secreted in cell-derived extracellular vesicles their mechanisms action explained. Furthermore, an overview presented, explaining main challenges therapies, providing potential solutions. In particular, a highlight use novel Muse cells, which bypasses conventional limitations. The paper concludes suggestions for directions future research.

Language: Английский

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Microenvironmental Modulation for Therapeutic Efficacy of Extracellular Vesicles

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Abstract Extracellular vesicles (EVs) hold significant promise for the prevention and treatment of various diseases. However, translation EV‐based therapies into clinical practice faces considerable challenges, particularly in terms production yield therapeutic efficacy. Recent studies have emphasized heterogeneity EVs influence parental cell microenvironmental signals on their biogenesis, cargo composition, outcomes. This review offers a comprehensive overview strategies to optimize efficacy through physical, biochemical, mechanical modulation. Additionally, it explores how affect EV cargoes mechanisms by which these can improve The also addresses current challenges potential solutions accelerate therapies. Ultimately, highlights modulation unlocking full capacity EVs, providing key insights use treating

Language: Английский

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AhR Activation at the Air-Blood Barrier Alters Systemic microRNA Release After Inhalation of Particulate Matter Containing Environmentally Persistent Free Radicals

Cardiovascular Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Language: Английский

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