The potential use of mesenchymal stem cells-derived exosomes as microRNAs delivery systems in different diseases

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Jan. 23, 2023

Abstract MicroRNAs (miRNAs) are a group of small non-coding RNAs that regulate gene expression by targeting mRNA. Moreover, it has been shown miRNAs changed in various diseases, such as cancers, autoimmune disease, infectious and neurodegenerative Diseases. The suppression miRNA function can be easily attained utilizing anti-miRNAs. In contrast, an enhancement achieved through the utilization modified mimetics. discovery appropriate carriers body become interesting subject for investigators. Exosomes (EXOs) therapeutic efficiency safety transferring different cellular biological components to recipient cell have attracted significant attention their capability carriers. Mesenchymal stem cells (MSCs) recognized generate wide range EXOs (MSC-EXOs), showing MSCs may effective EXO generation clinically measure compared other origins. MSC-EXOs widely investigated because immune attributes, tumor-homing flexible characteristics. this article, we summarized features MSC-EXOs, including production, purification, loading methods modification targeted delivery diseases. Graphical abstract

Language: Английский

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A Novel Superparamagnetic Multifunctional Nerve Scaffold: A Remote Actuation Strategy to Boost In Situ Extracellular Vesicles Production for Enhanced Peripheral Nerve Repair

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(3)

Published: Sept. 1, 2023

Abstract Extracellular vesicles (EVs) have inherent advantages over cell‐based therapies in regenerative medicine because of their cargos abundant bioactive cues. Several strategies are proposed to tune EVs production vitro. However, it remains a challenge for manipulation vivo, which poses significant difficulties EVs‐based that aim promote tissue regeneration, particularly long‐term treatment diseases like peripheral neuropathy. Herein, superparamagnetic nanocomposite scaffold capable controlling on‐demand is constructed by incorporating polyethyleneglycol/polyethyleneimine modified nanoparticles into polyacrylamide/hyaluronic acid double‐network hydrogel (Mag‐gel). The Mag‐gel highly sensitive rotating magnetic field (RMF), and can act as mechano‐stimulative platform exert micro/nanoscale forces on encapsulated Schwann cells (SCs), an essential glial cell supporting nerve regeneration. By switching the ON/OFF state RMF, scale up local SCs‐derived (SCs‐EVs) both vitro vivo. Further transcriptome sequencing indicates enrichment transcripts favorable axon growth, angiogenesis, inflammatory regulation SCs‐EVs with ultimately results optimized repair Overall, this research provides noninvasive remotely time‐scheduled method fine‐tuning accelerate including nerves.

Language: Английский

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Exosomes from preconditioned mesenchymal stem cells: Tissue repair and regeneration

Regenerative Therapy, Journal Year: 2024, Volume and Issue: 25, P. 355 - 366

Published: Feb. 14, 2024

As a prominent research area in tissue repair and regeneration, mesenchymal stem cells (MSCs) have garnered substantial attention for their potential the treatment of various diseases. It is now widely recognized that therapeutic effects MSCs primarily occur through paracrine mechanisms. Among these mechanisms, exosomes play crucial role by exerting series regulatory on surrounding tissues. While shown promise treating diseases, they do some limitations, such as limited secretion, poor targeting, single functionality. However, MSC preconditioning can enhance production exosomes, lead to more stable functionality improve effects. Moreover, could also serve carriers specific drugs or genes, enabling precise treatments This review summarizes most recent literatures how influences regenerative provides new insights into application derived from MSCs.

Language: Английский

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Advancements in extracellular vesicles biomanufacturing: a comprehensive overview of large-scale production and clinical research

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 19, 2025

Extracellular vesicles (EVs) are nano-sized, membranous structures secreted by cells into the extracellular space, have attracted considerable attention in field of biosciences for their role intercellular communication various physiological and pathological processes. Their ubiquitous presence bodily fluids cell-specific characteristics make them promising candidates as biomarkers. Additionally, ability to transport biological therapeutics across different barriers specific target underscores significant translational potential diagnostic therapeutic purposes. Significant progress has been achieved translation EVs research clinical applications, however, challenges persist large-scale production EVs, particularly areas scalable manufacturing, efficient isolation methods, drug loading techniques, advanced characterization technology. This review critically examines complex processes involved biogenesis explores recent developments production. By synthesizing knowledge from these fields, this aims provide a holistic perspective on evolving landscape its underscoring both accomplishments obstacles that lie ahead fully realizing biomedicine.

Language: 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, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

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Induced Pluripotent Stem Cell‐Derived Extracellular Vesicles Promote Wound Repair in a Diabetic Mouse Model via an Anti‐Inflammatory Immunomodulatory Mechanism

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(26)

Published: June 19, 2023

Abstract Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have recently been explored in clinical trials for treatment of diseases with complex pathophysiologies. However, production MSC EVs is currently hampered by donor‐specific characteristics and limited ex vivo expansion capabilities before decreased potency, thus restricting their potential as a scalable reproducible therapeutic. Induced pluripotent stem (iPSCs) represent self‐renewing source obtaining differentiated iPSC‐derived MSCs (iMSCs), circumventing both scalability donor variability concerns therapeutic EV production. Thus, it initially sought to evaluate the iMSC EVs. Interestingly, while utilizing undifferentiated iPSC control, found that vascularization bioactivity similar anti‐inflammatory superior donor‐matched cell‐based assays. To supplement this initial vitro screen, diabetic wound healing mouse model where pro‐vascularization activity these would be beneficial employed. In model, more effectively mediate inflammation resolution within bed. Combined lack additional differentiation steps required generation, results support use iPSCs respect efficacy.

Language: Английский

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Prospects and challenges of tissue-derived extracellular vesicles

Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(9), P. 2950 - 2978

Published: June 22, 2024

Extracellular vesicles (EVs) are considered a vital component of cell-to-cell communication and represent new frontier in diagnostics means to identify pathways for therapeutic intervention. Recently, studies have revealed the importance tissue-derived EVs (Ti-EVs), which present interstitial spaces between cells, as they better underlying physiology complex, multicellular tissue microenvironments biology disease. native, lipid bilayer membraned nano-sized particles produced by all cells that packaged with varied functional biomolecules including proteins, lipids, nucleic acids. They implicated short- long-range cellular may elicit responses recipient cells. To date, often utilized cultured or biological fluids source do not capture local molecular signatures microenvironment. Recent work utilizing Ti-EVs has elucidated novel biomarkers disease provided insights into mechanisms lead development agents. Still, there considerable challenges facing current studies. This review explores vast potential unique Ti-EV research provides considerations future seek advance this exciting field.

Language: Английский

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Mesenchymal stromal cell-derived extracellular vesicles therapy openings new translational challenges in immunomodulating acute liver inflammation

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 21, 2024

Inflammation plays a critical role in conditions such as acute liver failure, acute-on-chronic and ischemia-reperfusion-induced injury. Various pathogenic pathways contribute to inflammation, involving inflammatory polarization of macrophages Küpffer cells, neutrophil infiltration, dysregulation T cell subsets, oxidative stress, activation hepatic stellate cells. While mesenchymal stromal cells (MSCs) have demonstrated beneficial properties, their clinical translation is limited by cellular nature. However, MSC-derived extracellular vesicles (MSC-EVs) emerged promising cell-free therapeutic approach for immunomodulation. MSC-EVs naturally mirror parental overcoming the limitations associated with use MSCs. In vitro vivo preclinical studies that replicate effects MSCs This includes reduction death improvement hepatocyte function, induction immunomodulatory effects, mitigation cytokine storm. Nevertheless, face challenges regarding necessity defining consistent isolation methods, optimizing culture conditions, establishing quality control measures EV characterization functional assessment. By standardized protocols, guidelines, affordable cost mass production, clinicians researchers will solid foundation conduct further studies, validate efficacy MSC-EVs, ultimately pave way implementation

Language: Английский

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Advances in the application of extracellular vesicles derived from three-dimensional culture of stem cells

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 1, 2024

Abstract Stem cells (SCs) have been used therapeutically for decades, yet their applications are limited by factors such as the risk of immune rejection and potential tumorigenicity. Extracellular vesicles (EVs), a key paracrine component stem cell potency, overcome drawbacks cell-free therapeutic agent play an important role in treating various diseases. However, EVs derived from two-dimensional (2D) planar culture SCs low yield face challenges large-scale production, which hinders clinical translation EVs. Three-dimensional (3D) culture, given its ability to more realistically simulate vivo environment, can not only expand large quantities, but also improve activity EVs, changing content improving effects. In this review, we briefly describe advantages EV-related applications, provide overview 3D finally focus on specific future perspectives different SCs. Graphical

Language: Английский

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Adipose-Derived Stem Cell Exosomes Facilitate Diabetic Wound Healing: Mechanisms and Potential Applications

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 6015 - 6033

Published: June 1, 2024

Abstract: Wound healing in diabetic patients is frequently hampered. Adipose-derived stem cell exosomes (ADSC-eoxs), serving as a crucial mode of intercellular communication, exhibit promising therapeutic roles facilitating wound healing. This review aims to comprehensively outline the molecular mechanisms through which ADSC-eoxs enhance We emphasize biologically active molecules released by these and their involvement signaling pathways associated with inflammation modulation, cellular proliferation, vascular neogenesis, other pertinent processes. Additionally, clinical application prospects reported are also deliberated. A thorough understanding potential applications anticipated furnish theoretical groundwork for combating Keywords: diabetes, healing, ADSC-exos, tissue regeneration, skin cells,

Language: Английский

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