Non-stem cell-derived exosomes: a novel therapeutics for neurotrauma

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Март 12, 2024

Abstract Neurotrauma, encompassing traumatic brain injuries (TBI) and spinal cord (SCI) impacts a significant portion of the global population. While spontaneous recovery post-TBI or SCI is possible, recent advancements in cell-based therapies aim to bolster these natural reparative mechanisms. Emerging research indicates that beneficial outcomes such might be largely mediated by exosomes secreted from administered cells. stem cells have garnered much attention, derived non-stem cells, including neurons, Schwann microglia, vascular endothelial shown notable therapeutic potential. These contribute angiogenesis, neurogenesis, axon remodeling, display anti-inflammatory properties, marking them as promising agents for neurorestorative treatments. This review provides an in-depth exploration current methodologies, challenges, future directions regarding role cell-derived neurotrauma.

Язык: Английский

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Stem Cell-Derived Extracellular Vesicle-Mediated Therapeutic Signaling in Spinal Cord Injury

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 723 - 723

Опубликована: Янв. 16, 2025

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising therapeutic strategy for spinal cord injury (SCI). These nanosized possess unique properties such low immunogenicity and the ability to cross biological barriers, making them ideal carriers delivering bioactive molecules injured tissues. MSC-EVs been demonstrated exert multiple beneficial effects in SCI, including reducing inflammation, promoting neuroprotection, enhancing axonal regeneration. Recent studies delved into molecular mechanisms underlying MSC-EV-mediated effects. Exosomal microRNAs (miRNAs) identified key regulators of various cellular processes involved SCI pathogenesis repair. miRNAs can influence oxidative stress, apoptosis by modulating gene expression. This review summarized current state MSC-EV-based therapies highlighting potential clinical applications. We discussed challenges limitations translating these practice, inconsistent EV production, complex cargo composition, need targeted delivery strategies. Future research should focus on optimizing production characterization, identifying miRNAs, developing innovative systems maximize SCI.

Язык: Английский

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Static Topographical Cue Combined with Dynamic Fluid Stimulation Enhances the Macrophage Extracellular Vesicle Yield and Therapeutic Potential for Bone Defects

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Extracellular vesicles (EVs) hold promise for tissue regeneration, but their low yield and limited therapeutic efficacy hinder clinical translation. Bioreactors provide a larger culture surface area stable environment large-scale EV production, yet ability to enhance is limited. Physical stimulation, by inducing cell differentiation modulating cargo composition, offers more efficient, cost-effective, reproducible approach compared the loading of EVs biochemical priming parental cells. Herein, effects 3D-printed perfusion bioreactor with topographical cue on macrophage bioactivity were assessed. The results indicate that increased 12.5-fold enhanced in promoting osteogenic angiogenesis via upregulated miR-210-3p. Mechanistically, fluid shear stress activates Piezo1, triggering Ca2+ influx Yes-associated protein (YAP) nuclear translocation, secretion enhancing M2 polarization conjunction morphological changes guided aligned topography. Moreover, porous electrospun membrane-hydrogel composite scaffold loaded bioreactor-derived exhibited outstanding rat cranial defect model. This study presents scalable, platform production EVs, potentially overcoming key challenges translating EV-based therapies clinic.

Язык: Английский

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Extracellular particles: emerging insights into central nervous system diseases

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 1, 2025

Extracellular particles (EPs), including extracellular vesicles (EVs) and non-vesicular (NVEPs), are multimolecular biomaterials released by cells that play a crucial role in intercellular communication. Recently, new subtypes of EPs associated with central nervous system (CNS), such as exophers supermeres have been identified. These provide perspectives for understanding the pathological progression CNS disorders confer potential diagnostic value liquid biopsies neurodegenerative diseases (NDs). Moreover, emerged promising drug delivery vehicles targeted platforms CNS-specific therapies. In this review, we delineate landscape EP their roles pathophysiology diseases. We also review recent advances EP-based diagnosis NDs highlight importance analytical single-particle resolution exploitation biomarkers. Furthermore, summarize application engineered EVs treatment outline underexplored NVEPs novel therapeutic agents.

Язык: Английский

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Laminin-derived peptide, IKVAV, modulates macrophage phenotype through integrin mediation

Matrix Biology Plus, Год журнала: 2024, Номер 22, С. 100143 - 100143

Опубликована: Фев. 15, 2024

Macrophages are highly plastic immune cells known to exist on a spectrum of phenotypes including pro-inflammatory (M1) or pro-healing (M2). interact with extracellular matrix (ECM) ligands, such as fragments collagen and laminin. Interaction macrophages ECM ligands is mediated through integrin receptors. However, the role in directing macrophage function integrins not yet fully understood. Particularly, α2β1 has been implicated modulating function, but complexity mechanisms employed for integrin-ligation especially laminin-derived peptides makes it challenging understand macrophage-ECM interactions. We hypothesize that targeting peptide, IKVAV, will modulate phenotype. In this work we: i) investigated response IKVAV 2D 3D platform, ii) identified α2β1′s pertains modulation via IKVAV. Soluble treatment significantly reduced M1 markers increased M2 immunocytochemistry gene expression. While ECM-mimicking PEG-IKVAV hydrogels did have significant effects phenotype, we found dependent concentration peptide used duration exposure. To investigate integrin-ligand interactions macrophages, signaling was modulated by antagonists agonists. observed blocking reduces activation. leveraging therapeutic ability designing immunomodulatory solutions, critical elucidate IKVAV's mediating

Язык: Английский

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Unlocking the potential of exosomes: a breakthrough in the theranosis of degenerative orthopaedic diseases

Frontiers in Bioengineering and Biotechnology, Год журнала: 2024, Номер 12

Опубликована: Апрель 18, 2024

Degenerative orthopaedic diseases pose a notable worldwide public health issue attributable to the global aging population. Conventional medical approaches, encompassing physical therapy, pharmaceutical interventions, and surgical methods, face obstacles in halting or reversing degenerative process. In recent times, exosome-based therapy has gained widespread acceptance popularity as an effective treatment for diseases. This therapeutic approach holds potential "cell-free" tissue regeneration. Exosomes, membranous vesicles resulting from fusion of intracellular multivesicles with cell membrane, are released into extracellular matrix. Addressing challenges such rapid elimination natural exosomes vivo limitation drug concentration can be effectively achieved through various strategies, including engineering modification, gene overexpression biomaterial binding. review provides concise overview source, classification, preparation methods exosomes, followed by in-depth analysis their functions applications. Furthermore, explores strategies utilizing diseases, overexpression, The primary objective is provide fresh viewpoint on utilization addressing bone conditions support practical application theranosis

Язык: Английский

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Engineered Extracellular Vesicles: A potential treatment for regeneration

iScience, Год журнала: 2023, Номер 26(11), С. 108282 - 108282

Опубликована: Окт. 24, 2023

Extracellular vesicles (EVs) play a critical role in various physiological and pathological processes. EVs have gained recognition regenerative medicine due to their biocompatibility low immunogenicity. However, the practical application of faces challenges such as limited targeting ability, yield, inadequate therapeutic effects. To overcome these limitations, engineered emerged. This review aims comprehensively analyze engineering methods utilized for modifying donor cells EVs, with focus on comparing potential between natural EVs. Additionally, it investigate specific cell effects that crucial promoting repair regeneration, while also exploring underlying mechanisms involved field medicine.

Язык: Английский

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Exosomal ncRNAs: Multifunctional contributors to the immunosuppressive tumor microenvironment of hepatocellular carcinoma

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 173, С. 116409 - 116409

Опубликована: Март 8, 2024

Hepatocellular carcinoma (HCC) is a malignant liver cancer characterized by aggressive progression, unfavorable prognosis, and an increasing global health burden. Therapies that precisely target immunological checkpoints immune cells have gained significant attention as possible therapeutics in recent years. In truth, the efficacy of immunotherapy heavily contingent upon tumor microenvironment (TME). Recent studies indicated exosomes serve sophisticated means communication among biomolecules, executing essential part TME suppression. Exosomal non-coding RNAs (ncRNAs) can induce activation immunosuppressive suppress system, such cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), neutrophils (TANs), CD+8 T cells, regulatory (Tregs), B (Bregs). This cell-cell crosstalk triggered exosomal ncRNAs promotes proliferation metastasis, angiogenesis, phenotype transformation, drug resistance. Hence, it imperative to comprehend how regulate or within devise more comprehensive productive programs. study discusses features HCC redefines tumor's microenvironment, hence facilitating advancement HCC. Furthermore, we also explored potential viable biological natural vehicle for therapy.

Язык: Английский

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Chitosan‐Modified Hydrogel Microsphere Encapsulating Zinc‐Doped Bioactive Glasses for Spinal Cord Injury Repair by Suppressing Inflammation and Promoting Angiogenesis

Advanced Healthcare Materials, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 9, 2024

Spinal cord injury (SCI) is a common nerve caused by external force, resulting in sensory and motor impairments. Previous studies demonstrated that inhibiting the neuroinflammation promoted SCI repair. However, these approaches are low efficient, lack targeting specificity, even require repeated high doses of systemic administration. To address such issues, present study, chitosan-modified hydrogel microspheres encapsulating with zinc-doped bioactive glasses (CS-MG@Zn/BGs) constructed for targeted repair SCI. In vitro, CS-MG@Zn/BGs effectively inhibited acute inflammatory response initiated microglia angiogenic activities. vivo, injured site, attenuated infiltration modulating polarization toward M2 type. Furthermore, it facilitated vascular reconstruction, neuronal differentiation, axonal regeneration remyelination at thereby function recovery mice. The vitro vivo results implied may be promising alternative rehabilitation

Язык: Английский

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Hydrogel-encapsulated extracellular vesicles for the regeneration of spinal cord injury

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Дек. 14, 2023

Spinal cord injury (SCI) is a critical neurological condition that may impair motor, sensory, and autonomous functions. At the cellular level, inflammation, impairment of axonal regeneration, neuronal death are responsible for SCI-related complications. Regarding high mortality morbidity rates associated with SCI, there need effective treatment. Despite advances in SCI repair, an optimal treatment complete recovery after has not been found so far. Therefore, strategy needed to promote regeneration repair SCI. In recent years, regenerative treatments have become potential option achieving improved functional by promoting growth new neurons, protecting surviving preventing additional damage spinal cord. Transplantation cells cells-derived extracellular vesicles (EVs) can be recovery. However, some limitations challenges related cell-based strategies. Ethical concerns limited efficacy due low survival rate, immune rejection, tumor formation therapies. Using EVs helpful overcome these limitations. It should considered short half-life, poor accumulation, rapid clearance, difficulty targeting specific tissues EVs-based Hydrogel-encapsulated exosomes enhancing through maintaining their bioactivity, from facilitating sustained release at target site. These hydrogel-encapsulated neuroregeneration improving recovery, reducing This review aims provide overview current research status, challenges, future clinical opportunities

Язык: Английский

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