Extracellular vesicles as tools and targets in therapy for diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 5, 2024

Abstract Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers ubiquitously released from cells under normal pathological conditions. Human serum is a rich source of these EVs, though their isolation proteins non-EV lipid particles poses challenges. These transport various cellular components such as proteins, mRNAs, miRNAs, DNA, lipids across distances, influencing numerous physiological events, including those within tumor microenvironment (TME). Their pivotal roles in communication make EVs promising candidates for therapeutic agents, drug delivery systems, disease biomarkers. Especially cancer diagnostics, EV detection can pave way early identification offers potential diagnostic Moreover, subtypes emerging targeted tools, highlighting clinical significance. The need non-invasive biomarkers to monitor biological processes purposes remains unfulfilled. Tapping unique composition could unlock advanced avenues future. In this review, we discuss detail conditions, cancers (encompassing head neck, lung, gastric, breast, hepatocellular carcinoma), neurodegenerative disorders, diabetes, viral infections, autoimmune renal diseases, emphasizing advancements molecular diagnostics delivery.

Language: Английский

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Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool?

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(7)

Published: July 4, 2022

Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal multipotent differentiation. There is compelling evidence that therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental effectors play a crucial role in intercellular communication, existing body fluids cell supernatants. Since MSC-derived EVs retain function protocells have lower immunogenicity, they wide range prospective applications advantages over therapy. We describe some characteristics MSC-EVs, discuss immune regulation regeneration, emphasis molecular mechanism application MSC-EVs treatment fibrosis support tissue repair. also highlight current challenges clinical ways to overcome problem quality heterogeneity.

Language: Английский

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Potential Use of Exosomes as Diagnostic Biomarkers and in Targeted Drug Delivery: Progress in Clinical and Preclinical Applications

ACS Biomaterials Science & Engineering, Journal Year: 2021, Volume and Issue: 7(6), P. 2106 - 2149

Published: May 14, 2021

Exosomes are cell-derived vesicles containing heterogeneous active biomolecules such as proteins, lipids, mRNAs, receptors, immune regulatory molecules, and nucleic acids. They typically range in size from 30 to 150 nm diameter. An exosome's surfaces can be bioengineered with antibodies, fluorescent dye, peptides, tailored for small molecule large biologics. have enormous potential a drug delivery vehicle due enhanced biocompatibility, excellent payload capability, reduced immunogenicity compared alternative polymeric-based carriers. Because of targeting specificity, exosomes capable delivering their cargo exosome-recipient cells. Additionally, potentially act early stage disease diagnostic tools the exosome carries various protein biomarkers associated specific disease. In this review, we summarize recent progress on composition, biological characterization, isolation techniques. Finally, outline clinical applications preclinical advancement provide an outlook importance use targeted delivery, biomarker study, vaccine development.

Language: Английский

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Isolation of extracellular vesicles with combined enrichment methods

Journal of Chromatography B, Journal Year: 2021, Volume and Issue: 1169, P. 122604 - 122604

Published: Feb. 27, 2021

Extracellular vesicles (EVs) are currently of tremendous interest in many research disciplines and EVs have potential for development EV diagnostics or therapeutics. Most well-known single isolation methods their particular advantages disadvantages terms purity yield. Combining provides additional to improve the efficacy both This review assesses contribution using combined by performing a two-step systematic literature analysis from all papers applying year 2019. resulted an overview various being applied isolations. A second database was generated studies within first that fairly compared multiple determining yield after isolation. From these databases it is shown most used not per definition best based on yield, indicating more factors play role choice which method choose than only method. included ~60% isolations were performed with methods. The majority differential ultracentrifugation alone combination ultrafiltration. When determined clearly outperformed methods, regardless type starting material used. recommended point would be use size-exclusion chromatography since this method, especially when low-speed centrifugation, highest purity, while still providing reasonable

Language: Английский

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Extracellular vesicles from adipose tissue‐derived stem cells alleviate osteoporosis through osteoprotegerin and miR‐21‐5p

Journal of Extracellular Vesicles, Journal Year: 2021, Volume and Issue: 10(12)

Published: Oct. 1, 2021

Osteoporosis is one of the most common skeletal disorders caused by imbalance between bone formation and resorption, resulting in quantitative loss tissue. Since stem cell-derived extracellular vesicles (EVs) are growing attention as novel cell-free therapeutics that have advantages over parental cells, therapeutic effects EVs from adipose tissue-derived cells (ASC-EVs) on osteoporosis pathogenesis were investigated. ASC-EVs isolated a multi-filtration system based tangential flow filtration (TFF) characterized using transmission electron microscopy, dynamic light scattering, zeta potential, cytometry, cytokine arrays, enzyme-linked immunosorbent assay. rich growth factors cytokines related to metabolism mesenchymal cell (MSC) migration. In particular, osteoprotegerin (OPG), natural inhibitor receptor activator nuclear factor-κB ligand (RANKL), was highly enriched ASC-EVs. We found intravenous administration attenuated mice. Also, significantly inhibited osteoclast differentiation macrophages promoted migration marrow-derived MSCs (BM-MSCs). However, OPG-depleted did not show anti-osteoclastogenesis effects, demonstrating OPG critical for Additionally, small RNA sequencing data analysed identify miRNA candidates anti-osteoporosis effects. miR-21-5p through Acvr2a down-regulation. let-7b-5p reduced expression genes osteoclastogenesis. Finally, reached tissue after they injected intravenously, remained longer. OPG, miR-21-5p, inhibit reduce gene suggesting promising agents treatment.

Language: Английский

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Stem Cells and Exosomes: New Therapies for Intervertebral Disc Degeneration

Cells, Journal Year: 2021, Volume and Issue: 10(9), P. 2241 - 2241

Published: Aug. 29, 2021

Intervertebral disc degeneration (IVDD) occurs as a result of an imbalance the anabolic and catabolic processes in intervertebral disc, leading to alteration composition extracellular matrix (ECM), loss nucleus pulposus (NP) cells, excessive oxidative stress inflammation. Degeneration IVD naturally with age, but mechanical trauma, lifestyle factors certain genetic abnormalities can increase likelihood symptomatic disease progression. IVDD, often referred degenerative (DDD), poses increasingly substantial financial burden due aging population increasing incidence obesity United States. Current treatments for IVDD include pharmacological surgical interventions, these lack ability stop progression restore functionality IVD. Biological therapies have been evaluated show varying degrees efficacy reversing long-term. Stem cell-based shown promising results regeneration IVD, face both biological ethical limitations. Exosomes play important role intercellular communication, stem cell-derived exosomes maintain therapeutic benefit their origin cells without associated risks. This review highlights current state research on use stem-cell derived treatment IVDD.

Language: Английский

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Extracellular vesicles in kidney disease

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(8), P. 499 - 513

Published: May 31, 2022

Language: Английский

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Principles and Problems of Exosome Isolation from Biological Fluids

Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology, Journal Year: 2022, Volume and Issue: 16(2), P. 115 - 126

Published: June 1, 2022

Language: Английский

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Cartilage regeneration and inflammation modulation in knee osteoarthritis following injection of allogeneic adipose-derived mesenchymal stromal cells: a phase II, triple-blinded, placebo controlled, randomized trial

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 14, 2023

Abstract Background Intra-articular injection of mesenchymal stromal cells (MSCs) with immunomodulatory features and their paracrine secretion regenerative factors proposed a noninvasive therapeutic modality for cartilage regeneration in knee osteoarthritis (KOA). Methods Total number 40 patients KOA enrolled two groups. Twenty received intra-articular 100 × 10 6 allogeneic adipose-derived (AD-MSCs), 20 as control group placebo (normal saline). Questionnaire-based measurements, certain serum biomarkers, some cell surface markers were evaluated 1 year. Magnetic resonance imaging (MRI) before year after was performed to measure possible changes the articular cartilage. Results Forty allocated including 4 men (10%) 36 women (90%) average age 56.1 ± 7.2 years 52.8 7.5 AD-MSCs group. Four (two from group) excluded during study. Clinical outcome measures showed improvement Hyaluronic acid oligomeric matrix protein levels blood decreased significantly who ( P < 0.05). Although IL-10 level increased week 0.05), inflammatory dramatically 3 months 0.001). Expressions CD3, CD4, CD8 have decreasing trend 6-month follow-up 0.001), respectively. However, CD25 + remarkably treatment intervention 0.005). MRI findings slight increase thickness tibial femoral cartilages The significant medial posterior anterior areas ​​the tibia 0.01 0.05, Conclusion Inter-articular is safe. Laboratory data, findings, clinical examination at different time points notable Trial registration : Iranian registry trials (IRCT, https://en.irct.ir/trial/46 ), IRCT20080728001031N23. Registered 24 April 2018.

Language: Английский

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Mesenchymal stem cell-derived exosomes: Characteristics and applications in disease pathology and management

Life Sciences, Journal Year: 2024, Volume and Issue: 342, P. 122542 - 122542

Published: Feb. 28, 2024

Language: Английский

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