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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Mitochondria-Targeted Biomaterials-Regulating Macrophage Polarization Opens New Perspectives for Disease Treatment

International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 1509 - 1528

Опубликована: Фев. 1, 2025

Abstract: Macrophage immunotherapy is an emerging therapeutic approach designed for modulating the immune response to alleviate disease symptoms. The balance between pro-inflammatory and anti-inflammatory macrophages plays a pivotal role in progression of inflammatory diseases. Mitochondria, often referred as "power plants" cell, are essential organelles responsible critical functions such energy metabolism, material synthesis, signal transduction. functional state mitochondria closely linked macrophage polarization, prompting interest strategies that target regulate this process. To end, biomaterials with excellent targeting capabilities effective properties have been developed influence mitochondrial function polarization. However, comprehensive summary biomaterial-driven modulation control phenotypes still lacking. This review highlights polarization discusses mediated by biomaterials, including mitochondria-targeted biomaterials. Finally, prospects challenges use these explored, emphasizing their potential be translated clinic. It anticipated will serve valuable resource materials scientists clinicians development next-generation Keywords: macrophages,

Язык: Английский

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Exosome-loaded methacrylated silk fibroin hydrogel delays intervertebral disc degeneration by DKK2-mediated mitochondrial unfolded protein response

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 162191 - 162191

Опубликована: Март 1, 2025

Язык: Английский

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Revolutionizing cancer treatment via bioengineered extracellular vesicles: Exploring nanovesicles to fully synthetic solutions

Applied Materials Today, Год журнала: 2024, Номер 40, С. 102395 - 102395

Опубликована: Авг. 28, 2024

The prevalence of cancer on a global scale has necessitated the development various therapeutic approaches. However, effectiveness and safety existing methods often face some limitations. Nanotechnology emerged as solution, enabling design nanosystems that can effectively deliver drugs. These address challenges such low drug stability solubility, well lack tumor targetability. While nanomaterials offer advantages, certain nanoparticles have their own limitations, which prompted researchers to explore innovative delivery systems. One promising avenue is use extracellular vesicles (EVs), are natural secreted by cells. EVs possess biocompatibility, stability, targeting capabilities, making them ideal candidates for carriers. still remain in this field. include limited production yield, complexity, inefficient cargo loading, controlled release To overcome these challenges, been employing engineering techniques modify structures EVs, enhancing intrinsic properties. Surface modification hybrid systems combine with other shown potential addressing This review focuses landscape crucial role therapeutics diagnosis. It begins exploring biological functions properties EVs. Additionally, introduces strategies isolating shedding light methodologies used harvest minute entities. Finally, highlights biomedical applications bioengineering treatment.

Язык: Английский

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USP26 Combats Age‐Related Declines in Self‐Renewal and Multipotent Differentiation of BMSC by Maintaining Mitochondrial Homeostasis

Advanced Science, Год журнала: 2024, Номер 11(44)

Опубликована: Окт. 8, 2024

Abstract Age‐related declines in self‐renewal and multipotency of bone marrow mesenchymal stem cells (BMSCs) limit their applications tissue engineering clinical therapy. Thus, understanding the mechanisms behind BMSC senescence is crucial for maintaining rejuvenation multipotent differentiation capabilities BMSCs. This study reveals that impaired USP26 expression BMSCs leads to mitochondrial dysfunction, ultimately resulting aging age‐related Specifically, decreased results protein levels Sirtuin 2 due its ubiquitination degradation, which dysfunction multilineage potentials. Additionally, a result dampened hypoxia‐inducible factor 1α (HIF‐1α) expression. HIF‐1α facilitates transcriptional by increasing promoter activity through binding ‐191 — ‐198 bp ‐262 ‐269 regions on promoter. Therefore, identification as being correlated with BMSCs, along action mechanisms, suggests represents novel therapeutic target combating

Язык: Английский

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Palmatine activation of TFEB enhances autophagy and alleviates endoplasmic reticulum stress in intervertebral disc degeneration

Phytomedicine, Год журнала: 2025, Номер unknown, С. 156431 - 156431

Опубликована: Янв. 1, 2025

Язык: Английский

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Decidual mesenchymal stem cells derived extracellular vesicles regulate ferroptosis to alleviate intervertebral disc degeneration through the HIF-1α signaling pathway

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 161357 - 161357

Опубликована: Март 1, 2025

Язык: Английский

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Injectable Nanocomposite Hydrogels for Intervertebral Disc Degeneration: Combating Oxidative Stress, Mitochondrial Dysfunction, and Ferroptosis

Advanced Healthcare Materials, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Abstract Intervertebral disc degeneration (IVDD) is a major cause of low back pain, where oxidative stress and mitochondrial dysfunction are key contributors. Additionally, ferroptosis, an iron‐dependent form cell death, identified as critical mechanism in IVDD pathogenesis. Herein, the therapeutic potential gallic acid (GA)‐derived PGA‐Cu nanoparticles, enhanced with functional octapeptide (Cys‐Lys‐His‐Gly‐ d ‐Arg‐ ‐Tyr‐Lys‐Phe, SS08) to build mitochondria‐targeted nanoparticles (PGA‐Cu@SS08), embedded within hydrogel matrix nanocomposite hydrogel, explored. The show targeted localization mitochondria, effectively scavenging reactive oxygen species preserving function. abundant phenolic hydroxyl groups present on nanoparticle surface, along histidine residue SS08 peptide, endow these entities capacity chelate iron. Through RNA sequencing analysis, it discovered that PGA‐Cu@SS08 activates NRF2 signaling pathway, mitigating ferroptosis. It also reduces iron overload by inhibiting autophagy storage proteins. hydrogels exhibit excellent biocompatibility biodegradability, mechanical properties improve intervertebral (IVD) performance. continuously released from hydrogels, restoring IVD height maintaining tissue hydration levels, thus facilitating future applications for alleviating IVDD.

Язык: Английский

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Exosomes derived from MSCs exposed to hypoxic and inflammatory environments slow intervertebral disc degeneration by alleviating the senescence of nucleus pulposus cells through epigenetic modifications

Bioactive Materials, Год журнала: 2025, Номер 49, С. 515 - 530

Опубликована: Март 20, 2025

Язык: Английский

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Synergistic Modulating of Mitochondrial Transfer and Immune Microenvironment to Attenuate Discogenic Pain

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

Abstract Discogenic pain, caused by intervertebral disc degeneration (IVDD), is a prevalent and challenging condition to treat effectively. Macrophage infiltration with neural ectopic in‐growth resulting from structural disturbances within the (IVD) major cause of discogenic pain. This work systematically reveals how nanoparticles can synergistically regulate immune microenvironment mitochondrial communication attenuate The antioxidant metal‐polyphenol nanoparticle system sequentially macrophage phenotype delivery efficiency. strategy circumvents necessity for isolation preservation techniques that are typically required in conventional transplantation procedures. Furthermore, it facilitates effective sustained mitochondria damaged cells. In vivo, this formulation effectively preserves IVD height, maintains integrity nucleus pulposus (NP), restores pain thresholds. Thus, nanoplatform offers an approach traditional surgical treatments significant potential clinical application.

Язык: Английский

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