Hypoxia‐Preconditioned BMSC‐Derived Exosomes Induce Mitophagy via the BNIP3–ANAX2 Axis to Alleviate Intervertebral Disc Degeneration

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Июль 8, 2024

Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics autophagic flux. This study finds that absence BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) associated with senescence-related NPC degeneration, disrupting quality control. Bone marrow mesenchymal stem (BMSCs) have multidirectional differentiation potential produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3-rich NPCs, thereby alleviating aging-associated flux, promoting damaged clearance, restoring Mechanistically, BNIP3 shown interact membrane-bound annexin A2 (ANXA2), enabling liberation transcription factor EB (TFEB) from ANXA2-TFEB complex, TFEB nuclear translocation, regulating autophagy lysosomal gene activation. Furthermore, rat model IVDD established verified vivo efficacy exosomes repairing injuries, delaying aging, matrix (ECM) synthesis. In summary, hypoxia-induced BMSC alleviate by activating BNIP3/ANXA2/TFEB axis, providing new target for treatment.

Язык: Английский

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Exosomes from preconditioned mesenchymal stem cells: Tissue repair and regeneration

Regenerative Therapy, Год журнала: 2024, Номер 25, С. 355 - 366

Опубликована: Фев. 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.

Язык: Английский

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Extracellular vesicles are key players in mesenchymal stem cells’ dual potential to regenerate and modulate the immune system

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 207, С. 115203 - 115203

Опубликована: Фев. 9, 2024

MSCs are used for treatment of inflammatory conditions or regenerative purposes. complete cells and allogenic transplantation is in principle possible, but mostly autologous use preferred. In recent years, it was discovered that secrete extracellular vesicles. These active budded off vesicles carry a cargo. The cargo can be miRNA, protein, lipids etc. transported through the body fuse with target cells. Thereby, they influence phenotype modulate disease. have, like MSCs, immunomodulatory capacities. This review will focus on those features discuss their dual role. Besides immunomodulation, regeneration concentrate bone, cartilage, tendon, vessels nerves. Current clinical trials immunomodulation started last five years highlighted as well. summary, have great potential disease modulating entity treatment. Their characteristics need to taken into account often both important having best effect.

Язык: Английский

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Mesenchymal stem cell-derived exosomes: a promising alternative in the therapy of preeclampsia

Stem Cell Research & Therapy, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 5, 2024

Abstract Preeclampsia (PE) is a common morbid complication during pregnancy, affecting 2%-8% of pregnancies globally and posing serous risks to the health both mother fetus. Currently, only effective treatment for PE timely termination which comes with increased perinatal risks. However, there no way delay pathological progress improve maternal fetal outcomes. In light this, it great significance seek therapeutic strategies PE. Exosomes are nanoparticles carrying bioactive substances such as proteins, lipids, nucleic acids, have emerged novel vehicle intercellular communication. Mesenchymal stem cell-derived exosomes (MSC-Exos) participate in various important physiological processes, including immune regulation, cell proliferation migration, angiogenesis, shown promising potential tissue repair disease treatment. Recently, MSC-Exos therapy has gained popularity ischaemic diseases, dysfunction, inflammatory other fields due their minimal immunogenicity, characteristics similar donor cells, ease storage, low risk tumor formation. This review elaborates on mechanism treating preeclampsia, considering main pathogenic factors condition, placental vascular dysplasia, immunological disorders, oxidative stress, based biological function MSC-Exos. Additionally, we discuss depth advantages challenges acellular agent preeclampsia

Язык: Английский

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Exosomal miR-3174 induced by hypoxia promotes angiogenesis and metastasis of hepatocellular carcinoma by inhibiting HIPK3

iScience, Год журнала: 2024, Номер 27(2), С. 108955 - 108955

Опубликована: Янв. 19, 2024

Hepatocellular carcinoma (HCC) is a highly malignant tumor with rich blood supply. HCC-derived exosomes containing hereditary substances including microRNAs (miRNAs) were involved in regulating angiogenesis and metastasis. Subsequently, series experiments performed to evaluate the effect of exosomal miR-3174 on HCC was ingested by human umbilical vein endothelial cells (HUVECs) which HIPK3 targeted silenced, causing subsequent inhibition Fas p53 signaling pathways. Furthermore, induced permeability HUVECs enhance progression Under hypoxia, upregulated HIF-1α further promoted transcription miR-3174. Moreover, HNRNPA1 augmented package into exosomes. Clinical data analysis confirmed that patients high-level correlated worse prognosis. Thus, hypoxia promotes metastasis inhibiting HIPK3/p53 HIPK3/Fas Our findings might provide potential targets for anti-tumor therapy.

Язык: Английский

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TGF-β1 mediates hypoxia-preconditioned olfactory mucosa mesenchymal stem cells improved neural functional recovery in Parkinson’s disease models and patients

Military Medical Research, Год журнала: 2024, Номер 11(1)

Опубликована: Июль 22, 2024

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in substantia nigra (SN). Activation neuroinflammatory response has pivotal role PD. Mesenchymal stem cells (MSCs) have emerged as promising therapeutic approach for various nerve injuries, but there are limited reports on their use PD and underlying mechanisms remain unclear. Methods We investigated effects clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs neural functional recovery both models patients, well preventive mouse To assess improvement induced hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay transposase accessible chromatin with high-throughput (ATAC-seq) combined full-length transcriptome isoform-sequencing (ISO-seq), assay. Furthermore, present findings from an initial cohort patients enrolled phase I first-in-human clinical trial evaluating safety efficacy intraspinal transplantation hOM-MSC into severe patients. Results A identified that transforming growth factor-β1 (TGF-β1), secreted hOM-MSCs, played critical modulating mitochondrial function neurons. This effect was achieved through improving microglia immune regulation autophagy homeostasis SN, which closely associated responses. Mechanistically, exposure to led neuroinflammation partially mediated TGF-β1 via activation anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway located SN improved neurologic regulated without any adverse reactions observed Conclusions These provide compelling evidence involvement mediating beneficial Treatment prevention could be effective neuroprotective strategy Additionally, may used alone or therapy treating

Язык: Английский

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Isolation, identification, and challenges of extracellular vesicles: emerging players in clinical applications

APOPTOSIS, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 10, 2024

Язык: Английский

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Insight in Hypoxia-Mimetic Agents as Potential Tools for Mesenchymal Stem Cell Priming in Regenerative Medicine

Stem Cells International, Год журнала: 2022, Номер 2022, С. 1 - 24

Опубликована: Март 26, 2022

Hypoxia-mimetic agents are new potential tools in MSC priming instead of hypoxia incubators or chambers. Several pharmaceutical/chemical hypoxia-mimetic can be used to induce the tissues: deferoxamine (DFO), dimethyloxaloylglycine (DMOG), 2,4-dinitrophenol (DNP), cobalt chloride (CoCl2), and isoflurane (ISO). increase cell proliferation, preserve enhance differentiation potential, migration neovascularization a concentration- stem source-dependent manner. Moreover, may HIF-1α, changing metabolism enhancing glycolysis like hypoxia. So, there is clear evidence that treatment with beneficial regenerative medicine, preserving capacities. These not studied so wildly as but, considering low cost ease use, believed find application pretreatment many diseases such ischemic heart disease myocardial fibrosis promote cardiac cartilage regeneration. The knowledge critical evaluating safety procedures use clinics. In this review, similarities differences between terms their therapeutic efficiency considered detail. advantages, challenges, future perspectives mimetic also discussed.

Язык: Английский

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Scalable Generation of Nanovesicles from Human-Induced Pluripotent Stem Cells for Cardiac Repair

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(22), С. 14334 - 14334

Опубликована: Ноя. 18, 2022

Extracellular vesicles (EVs) from stem cells have shown significant therapeutic potential to repair injured cardiac tissues and regulate pathological fibrosis. However, scalable generation of derived EVs for clinical utility remains a huge technical challenge. Here, we report rapid size-based extrusion strategy generate EV-like membranous nanovesicles (NVs) easily sourced human iPSCs in large quantities (yield 900× natural EVs). NVs isolated using density-gradient separation (buoyant density 1.13 g/mL) are spherical shape morphologically intact readily internalised by cardiomyocytes, primary fibroblasts, endothelial cells. captured the dynamic proteome parental include pluripotency markers (LIN28A, OCT4) regulators processes, including tissue (GJA1, HSP20/27/70, HMGB1), wound healing (FLNA, MYH9, ACTC1, ILK), stress response/translation initiation (eIF2S1/S2/S3/B4), hypoxia response (HMOX2, HSP90, GNB1), extracellular matrix organization (ITGA6, MFGE8, ITGB1). Functionally, significantly promoted tubule formation (angiogenesis) (p < 0.05) survival cardiomyocytes exposed low oxygen conditions (hypoxia) 0.0001), as well attenuated TGF-β mediated activation fibroblasts 0.0001). Quantitative profiling target cell following NV treatments revealed upregulation angiogenic proteins (MFGE8, MYH10, VDAC2) pro-survival (CNN2, THBS1, IGF2R) cardiomyocytes. In contrast, TGF-β-driven remodelling capacity (ACTN1, COL1A1/2/4A2/12A1, ITGA1/11, THBS1). This study presents approach generating functional repair.

Язык: Английский

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Extracellular vesicle-transmitted miR-671-5p alleviates lung inflammation and injury by regulating the AAK1/NF-κB axis

Molecular Therapy, Год журнала: 2023, Номер 31(5), С. 1365 - 1382

Опубликована: Фев. 2, 2023

Mesenchymal stem cells regulate remote intercellular signaling communication via their secreted extracellular vesicles. Here, we report that menstrual blood-derived alleviate acute lung inflammation and injury vesicle-transmitted miR-671-5p. Disruption of this abundantly expressed miR-671-5p dramatically reduced the ameliorative effect vesicles released by on lipopolysaccharide (LPS)-induced pulmonary inflammatory injury. Mechanistically, directly targets kinase AAK1 for post-transcriptional degradation. is found to positively activation nuclear factor κB (NF-κB) controlling stability inhibitory protein IκBα. This study identifies a potential molecular basis how derived from mesenchymal improve highlights functional importance miR-671-5p/AAK1 axis in progression diseases. More importantly, provides promising cell-based approach treatment disorders through an vesicle-dependent pathway.

Язык: Английский

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