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Engineered mesenchymal stem cell-derived exosomes: A revolutionary approach to unlocking liver disease treatment.

Exosomes, a specific type of extracellular vesicle with diameters ranging from 30 to 150 nm, play a vital role in coordinating various physiological and pathological processes through direct cell-to-cell communication. These vesicles transport a diverse range of molecules, including proteins, mRNAs, miRNAs, and lipids, that originate from parent cells. Exosomes are released by nearly all cell types, including mesenchymal stem cells (MSCs), and possess significant potential due to their regenerative and immunomodulatory properties. In the context of liver disease treatment, these capabilities o

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… These exosomes originate from the inward budding of the plasma membrane, leading to the formation of early endosomes, which then mature into multivesicular bodies (MVBs). Upon fusion of MVBs with the plasma membrane, exosomes are released into the extracellular space. … Exosome formation is thought to occur in three stages, starting with endocytic vesicles formed from cell membrane invagination, then the formation of multivesicular bodies (MVBs) from endocytic vesicles, and finally, exosome release through fusion with the cell membrane. …

m6A reader hnRNPA2B1 drives multiple myeloma osteolytic bone disease.

Rationale: Bone destruction is a hallmark of multiple myeloma (MM) and affects more than 80% of patients. Although previous works revealed the roles of N6-methyladenosine (m6A) reader hnRNPA2B1 in the development of tumors, whether hnRNPA2B1 regulates bone destruction in MM is still unknown. Methods: Alizarin red S staining, TRAP staining, ELISA and quantitative real-time PCR assays were used to evaluate osteogenesis and osteoclastogenesis in vitro. X ray and bone histomorphometric analysis were preformed to identify bone resorption and bone formation in vivo. Exosome isolation and characteriz

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… Exosomes are small membrane vesicles (30-150 nm) derived from the luminal membranes of multivesicular bodies. …

Research progress on exosomes derived from mesenchymal stem cells in hematological malignancies.

Mesenchymal stem cells (MSCs) are a subset of multifunctional stem cells with self-renewal and multidirectional differentiation properties that play a pivotal role in tumor progression. MSCs are reported to exert biological functions by secreting specialized vesicles, known as exosomes, with tumor cells. Exosomes participate in material and information exchange between cells and are crucial in multiple physiological and pathological processes. This study provides a comprehensive overview of the roles, mechanisms of action and sources of MSC exosomes in hematological malignancies, and different

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… Late endonucleosomes containing ILVs are generated, known as multivesicular bodies (MVBs). Mature MVBs are degraded after binding to lysosomes or fused with cell membranes to release ILVs to the extracellular environment via exocytosis. …

Перенос Митохондрии для ремонта миелина.

Обезвоживание является общей характеристикой нейро-воспалительных и дегенеративных заболеваний центральной нервной системы (КНС), таких, как множественный склероз (МС). Часто это связано с нарушениями межклеточной связи, биоэнергетики и метаболического баланса в сочетании с митохондриальной дисфункцией в таких клетках, как олигодендроциты, нейроны, астроциты и микроглиа. Несмотря на то, что нынешние методы лечения MS сосредоточены на иммуномодуляции, они не могут остановить или обратить вспять прогресс демиэлизации. Последние достижения подчеркивают межклеточный митохондриальный обмен в качест

Sphingolipid metabolism and hematologic disorders: current understanding and future directions.

Sphingolipids are not only key structural components of cell membranes but also serve as important signaling molecules, and their metabolic homeostasis is essential for the maintenance of cellular functions. In recent years, with the advancement of technologies such as metabolomics, studies have revealed that sphingolipid metabolic abnormalities are extensively involved in the occurrence and development of various hematological disorders, including immune thrombocytopenia, myeloproliferative neoplasms, graft-versus-host disease, hereditary hematological diseases, and hematologic malignancies.

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… Recent studies have revealed a central function for ceramide in regulating lysosomal integrity, multivesicular body (MVB) maturation, and exosome release. In various cell types, the accumulation of ceramide has been shown to influence lysosomal integrity and function ( Yuyama et al., 2020 ). … Diagram illustrating the formation of ceramide in the Golgi, its role in intraluminal vesicle generation within multivesicular bodies, exosome release, and downstream impacts including altered gene expression, immune cell activation, tumor microenvironment remodeling, and effects on leukemia cells, with …

Четвертое Международное совещание ИСЕВ, ISEV2015.

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… The absence of PrP C causes a delay in caveolin-mediated endocytosis and in the traffic of EGF-EGFR to late endosomes/multivesicular bodies (LE/MVB). … bodies (MVBs) fusion with the plasma membrane. …

Conditioned Media-Derived Tumor Extracellular Vesicles: Bridging Molecular Insights and Therapeutic Applications in Oncology.

Tumor-derived extracellular vesicles (EVs) are major mediators of oncogenic intercellular communication. However, many studies using conditioned media (CM) recover operationally defined EV- or small EV-enriched fractions rather than biogenesis-proven exosomes. This review synthesizes evidence from CM-derived tumor EV studies and aligns their biological interpretation with current EV nomenclature, characterization, and reporting principles. We first discuss exosome biogenesis as a defined endosomal pathway and then examine how CM collection, serum handling, culture format, oxygen tension, condi

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… When the term exosome is biogenetically justified, it refers to a biogenesis‐defined EV subset generated through the endosomal pathway: endocytosis gives rise to early endosomes, late endosomes, and multivesicular bodies (MVBs) containing intraluminal vesicles (ILVs), which can be released extracellularly … Endocytosis at the plasma membrane leads to the formation of early endosomes, which mature into late endosomes and multivesicular bodies (MVBs). …

Recent Innovations and Nano-Delivery of Actinium-225: A Narrative Review.

The actinium-225 (225Ac) radioisotope exhibits highly attractive nuclear properties for application in radionuclide therapy. However, the 225Ac radionuclide presents multiple daughter nuclides in its decay chain, which can escape the targeted site, circulate in plasma, and cause toxicity in areas such as kidneys and renal tissues. Several ameliorative strategies have been devised to circumvent this issue, including nano-delivery. Alpha-emitting radionuclides and nanotechnology applications in nuclear medicine have culminated in major advancements that offer promising therapeutic possibilities

Amiloride ameliorates muscle wasting in cancer cachexia through inhibiting tumor-derived exosome release.

BACKGROUND: Cancer cachexia (CAC) reduces patient survival and quality of life. Developments of efficient therapeutic strategies are required for the CAC treatments. This long-term process could be shortened by the drug-repositioning approach which exploits old drugs approved for non-cachexia disease. Amiloride, a diuretic drug, is clinically used for treatments of hypertension and edema due to heart failure. Here, we explored the effects of the amiloride treatment for ameliorating muscle wasting in murine models of cancer cachexia. METHODS: The CT26 and LLC tumor cells were subcutaneously in

Effects of Physical Cues on Stem Cell-Derived Extracellular Vesicles toward Neuropathy Applications.

The peripheral nervous system undergoes sufficient stress when affected by diabetic conditions, chemotherapeutic drugs, and personal injury. Consequently, peripheral neuropathy arises as the most common complication, leading to debilitating symptoms that significantly alter the quality and way of life. The resulting chronic pain requires a treatment approach that does not simply mask the accompanying symptoms but provides the necessary external environment and neurotrophic factors that will effectively facilitate nerve regeneration. Under normal conditions, the peripheral nervous system self-r

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… Once organized within late-endosome development, the Golgi apparatus then supplies ILVs with major histocompatibility complex (MHC) class I and II molecules, growth factor receptors, and RNAs, encompassed by multivesicular bodies (MVBs) [ 233 , 236 ]. … bodies | 2D | Two-dimensional NA | Nicotinic acid | 3D | Three-dimensional Na + | Sodium | | Author Contributions Writing—original draft preparation, D.B.; Writing—review and editing, J.E., A.N., M.S., Y.L. and C.Z.; Project administration, Y.L. and C.Z.; Funding acquisition, Y.L. and C.Z. …

Navigating the Landscape of Exosomal microRNAs: Charting Their Pivotal Role as Biomarkers in Hematological Malignancies.

Under physiological and pathological conditions, all cells release extracellular vesicles named exosomes, which act as transporters of lipidic, protein, and genetic material from parent to recipient cells. Neoplastic cells can secrete higher number of exosomes to exert pro-tumoral effects such as microenvironmental changes, disease progression, immunosuppression and drug-resistance. This holds true for both organ-specific cancers and hematologic malignancies. One of the most important components of exosomal cargo are microRNAs which can mediate all the abovementioned effects. More specifically

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… They originate from multivesicular bodies (MVBs) located in the cellular endosomal compartment and are released externally after MVBs fusion with cell membrane. For this reason, exosomes present some endosome-associated proteins on their surface (such as TSG101 and ALIX) [ 6 ]. … These formations are called multivesicular bodies (MVBs). …

Current trends in theranostic applications of extracellular vesicles in cancer.

BackgroundExtracellular vesicles (EVs) play an integral role in cancer biology, influencing tumor progression, metastasis, and tumor microenvironment. Due to their distinctive molecular composition, including proteins, nucleic acids, and lipids, EVs present a promising candidate for cancer diagnostics and precision therapeutics.MethodsThis review was conducted by looking up recent studies obtained through PubMed, Scopus, and Web of Science databases using targeted keywords such as "Extracellular Vesicles," "Cancer Therapy," "Biomarkers," "Exosomes," "Tumor Microenvironment," and "Precision Med

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… In contrast, exosomes are nanoscale vesicles that are produced from multivesicular bodies (MVBs) within late endosomes as shown in Figure 1 ( 21 ). Figure 1 Biogenesis and Fate of Exosomes. … These early endosomes mature into multivesicular bodies (MVBs) containing intraluminal vesicles. …

The Role of Extracellular Vesicles in Bone Regeneration and Associated Bone Diseases.

Extracellular vesicles (EVs) are nanoscale particles with a lipid bilayer membrane structure secreted by various cell types. Nearly all human cells secrete EVs, primarily mediating intercellular communication. In recent years, scientists have discovered that EVs can carry multiple biological cargos, such as DNA, non-coding RNAs (ncRNAs), proteins, cytokines, and lipids, and mediate intercellular signal transduction. Bone is a connective tissue with a nerve supply and high vascularization. The repair process after injury is highly complex, involving interactions among multiple cell types and bi

Interferon-Based Biopharmaceuticals: Overview on the Production, Purification, and Formulation.

The advent of biopharmaceuticals in modern medicine brought enormous benefits to the treatment of numerous human diseases and improved the well-being of many people worldwide. First introduced in the market in the early 1980s, the number of approved biopharmaceutical products has been steadily increasing, with therapeutic proteins, antibodies, and their derivatives accounting for most of the generated revenues. The success of pharmaceutical biotechnology is closely linked with remarkable developments in DNA recombinant technology, which has enabled the production of proteins with high specific

Acoustically-Activated Liposomal Nanocarriers to Mitigate the Side Effects of Conventional Chemotherapy with a Focus on Emulsion-Liposomes.

To improve currently available cancer treatments, nanomaterials are employed as smart drug delivery vehicles that can be engineered to locally target cancer cells and respond to stimuli. Nanocarriers can entrap chemotherapeutic drugs and deliver them to the diseased site, reducing the side effects associated with the systemic administration of conventional anticancer drugs. Upon accumulation in the tumor cells, the nanocarriers need to be potentiated to release their therapeutic cargo. Stimulation can be through endogenous or exogenous modalities, such as temperature, electromagnetic irradiati

Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications.

The insufficient and unspecific target of traditional therapeutic approaches in cancer treatment often leads to therapy resistance and cancer recurrence. Over the past decades, accumulating discoveries about stem cell biology have provided new potential approaches to cure cancer patients. Stem cells possess unique biological actions, including self-renewal, directional migration, differentiation, and modulatory effects on other cells, which can be utilized as regenerative medicine, therapeutic carriers, drug targeting, and generation of immune cells. In this review, we emphasize the mechanisms

Aberrant NSUN2-mediated m5C modification of exosomal LncRNA MALAT1 induced RANKL-mediated bone destruction in multiple myeloma.

The impact of exosome-mediated crosstalk between multiple myeloma (MM) cells and osteoclasts (OCs) on bone lesions remains to be investigated. Here, we identified NSUN2 and YBX1-mediated m5C modifications upregulated LncRNA MALAT1 expression in MM cells, which could be transported to OCs via exosomes and promote bone lesions. Methodologically, RNA-seq was carried out to detect the cargoes of exosomes. TRAP staining and WB were used to evaluate osteoclastogenesis in vitro. Micro-CT and bone histomorphometric analyses were performed to identify bone destruction in vivo. RNA pull-down, RIP, MeRIP

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… They originate from intracellular multivesicular bodies and are released into the extracellular microenvironment by exocytosis, acting as signal transducers or messengers in cell–cell communication for the changing phenotypes in recipient cells 11 , 12 . …

The Fifth International Meeting of ISEV, ISEV2016, Rotterdam, The Netherlands, 4 - 7 May, 2016.

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Cell-Selective Altered Cargo Properties of Extracellular Vesicles Following In Vitro Exposures to Intermittent Hypoxia.

Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is associated with cardiovascular and metabolic dysfunction. However, the mechanisms underlying these morbidities remain poorly delineated. Extracellular vesicles (EVs) mediate intercellular communications, play pivotal roles in a multitude of physiological and pathological processes, and could mediate IH-induced cellular effects. Here, the effects of IH on human primary cells and the release of EVs were examined. Microvascular endothelial cells (HMVEC-d), THP1 monocytes, THP1 macrophages M0, THP1 macrophages M1, THP1 macr

NK3.3-Derived Extracellular Vesicles Penetrate and Selectively Kill Treatment-Resistant Tumor Cells.

Cancer treatments often become ineffective due to the development of tumor resistance, leading to metastasis and relapse. Treatments may also fail because of their inability to access cells deep within the tumor tissue. When this occurs, new therapeutic agents are needed. We previously reported that NK3.3EVs, extracellular vesicles (EVs) derived from the normal human natural killer (NK) cell line, NK3.3, have strong cytotoxic activity against leukemia and breast cancer cell lines, without harming normal cells. Here, we used a three-dimensional (3D) MCF7 breast cancer mammosphere model to repro

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… NK EVs contain the cytolytic proteins found in NK granules (granzymes A, B, perforin, and NKLAM/RNF19b), indicating that both NK granules and EVs share a common biogenesis from multivesicular bodies. …