Bone marrow mesenchymal stem cells modulate miR-202-3p to suppress neuronal apoptosis following spinal cord injury through autophagy activation via the AMPK, MAPK, and PI3K/AKT/mTOR signaling pathway DOI Creative Commons
Ke Huang, Jing Fang,

Weiming Sun

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 3, 2024

Bone marrow mesenchymal stem cells (BMMSCs) have garnered attention as promising therapeutic modalities for spinal cord injury (SCI) due to their neuroregenerative, anti-apoptotic, and functional recovery-enhancing properties. The central role of microRNAs (miRNAs) in mediating the beneficial outcomes resulting from BMMSCs SCI has been highlighted recent studies, suggesting that targeted modulation specific miRNAs holds potential augmenting recovery. Our previous investigation implicated miR-202-3p reparative processes injured cords, although precise mechanistic underpinnings remain elusive. In vivo, were administered rats, while vitro, was transfected into PC-12 cells. Motor capabilities recovery assessed via Basso-Beattie-Bresnahan (BBB) scores footprinting tests; evaluation neuronal tissue repair conducted using Nissl staining, TUNEL hematoxylin eosin (HE) immunofluorescence; impacts on cellular autophagy, apoptosis, relevant pathways evaluated Western blotting, quantitative polymerase chain reaction (qPCR), transmission electron microscopy (TEM). Functionally, utilized improve motor rats. Histopathologically, they contributed damaged cords regeneration nerve axons. At molecular level, stimulated autophagy suppressed apoptosis by regulating AMPK, MAPK, PI3K/AKT/mTOR pathway. Collectively, our findings demonstrate coordinate inhibit mTOR activation PI3K/AKT pathways, thereby promoting TFEB dephosphorylation, modulating ultimately fostering post-SCI.

Language: Английский

Pyroptosis: candidate key targets for mesenchymal stem cell-derived exosomes for the treatment of bone-related diseases DOI Creative Commons
Hong Li, Peng Zhang, Minghui Lin

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 12, 2025

Bone-related diseases impact a large portion of the global population and, due to their high disability rates and limited treatment options, pose significant medical economic challenges. Mesenchymal stem cells (MSCs) can differentiate into multiple cell types offer strong regenerative potential, making them promising for treating various diseases. However, issues with immune response survival limit effectiveness transplantation. This has led increased interest in cell-free therapy, particularly use exosomes, which is most studied form this approach. Exosomes are extracellular vesicles that contain proteins, lipids, nucleic acids play key role communication material exchange. Pyroptosis, death involved innate immunity, also associated many Studies have shown MSC-derived exosomes therapeutic potential range conditions by regulating inflammation pyroptosis. study explored modulating pyroptosis improve bone-related

Language: Английский

Citations

2
Novel Insights into Neuroinflammatory Mechanisms in Traumatic Brain Injury: Focus on Pattern Recognition Receptors as Therapeutic Targets DOI

Harapriya Baral,

Ravinder K. Kaundal

Cytokine & Growth Factor Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
Pre-treated Mesenchymal Stem Cell-Derived Exosomes: A New Perspective for Accelerating Spinal Cord Injury Repair DOI Creative Commons

Zhiqiang Liao,

Jinwei Zeng,

Aiqing Lin

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 992, P. 177349 - 177349

Published: Feb. 5, 2025

Spinal cord injury (SCI) is a devastating event for the central nervous system (CNS), often resulting in loss of sensory and motor functions. It profoundly affects both physiological psychological well-being patients, reducing their quality life while also imposing significant economic pressure on families healthcare system. Due to complex pathophysiology SCI, effective treatments promoting recovery remain scarce. Mesenchymal stem cell-derived exosomes (MSC-Exos) offer advantages such as low immunogenicity, good biocompatibility, ability cross blood-spinal barrier (BSCB). In preclinical studies, they have progressively shown efficacy SCI repair functional recovery. However, yield insufficient targeting MSC-Exos limit therapeutic efficacy. Currently, genetic engineering other preprocessing techniques are being employed optimize properties exosomes, thereby enhancing potential. Therefore, this paper provides an overview biogenesis exosomes. summarizes current approaches optimizing exosome performance. Additionally, it details mechanisms through which optimized provide neuroprotection explores potential combined involving hydrogels.

Language: Английский

Citations

0
Harnessing stem cell-derived exosomes: a promising cell-free approach for spinal cord injury DOI Creative Commons
Miaoman Lin,

Farzaneh Alimerzaloo,

Xingjin Wang

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 17, 2025

Abstract Spinal cord injury (SCI) is a severe to the central nervous system that often results in permanent neurological dysfunction. Current treatments have limited efficacy and face challenges restoring function after injury. Recently, stem cell-derived exosomes gained attention as an experimental treatment for SCI due their unique properties, including superior biocompatibility, minimal immunogenicity non-tumorigenicity. With potential cell-free therapy, promote repair by enhancing nerve regeneration, reducing inflammation stabilizing blood-spinal barrier. This review summarizes advances exosome research over past years, focusing on mechanisms future prospects. Despite promising therapeutic potential, clinical translation remains challenging standardization of isolation protocols, compositional consistency long-term safety profiles require further investigation.

Language: Английский

Citations

0
Exploring the mechanism of bone marrow mesenchymal stromal cell exosomes in respiratory syncytial virus infection based on miRNA sequencing DOI Creative Commons
Bing Yao, Jinglei Liu, Zexiang Li

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 21, 2025

The role of Bone marrow mesenchymal stem cells (BMSCs) and their exosomes in regulating the host response to viral infections has garnered significant attention, yet research on specific mechanisms respiratory syncytial virus (RSV) infection remains limited. This study analyzes changes cytokine levels exosomal miRNA expression profiles BMSCs supernatants following RSV infection. findings reveal that leads a decrease IL-4 supernatants, alongside notable increases IL-6, IL-12, IFN-γ levels. Additionally, expressions F protein, G N gene were detected exosomes. Further vivo experiments demonstrated from RSV-treated significantly enhanced inflammatory RSV-infected mice, indicated by elevated serum cytokines, lung dysfunction, airway inflammation, increased mucus secretion. In contrast, untreated showed minimal effects inflammation damage infected mice. sequencing analysis identified differential miRNAs enriched multiple key signaling pathways, suggesting alters functional characteristics exosomes, shifting anti-inflammatory repair pro-inflammatory function. transformation may be mediated profile.

Language: Английский

Citations

0
Progression of mesenchymal stem cell regulation on imbalanced microenvironment after spinal cord injury DOI Creative Commons
Yifan Liu, Chenxi Zhao,

Rong Zhang

et al.

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 1, 2024

Language: Английский

Citations

3
Repair of spinal cord injury by bone marrow mesenchymal stem cell-derived exosomes: a systematic review and meta-analysis based on rat models DOI Creative Commons

Zhongduo Ye,

Yukun Zheng, Ningning Li

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Aug. 7, 2024

Objective This study aims to systematically evaluate the efficacy of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exo) in improving spinal cord injury (SCI) mitigate risk translational discrepancies from animal experiments clinical applications. Methods We conducted a comprehensive literature search up March 2024 using PubMed, Embase, Web Science, and Scopus databases. Two researchers independently screened literature, extracted data, assessed quality studies. Data analysis was performed STATA16 software. Results A total 30 studies were included. The results indicated that BMSCs-Exo significantly improved BBB score SCI rats (WMD = 3.47, 95% CI [3.31, 3.63]), inhibited expression pro-inflammatory cytokine TNF- α (SMD -3.12, [−3.57, −2.67]), promoted anti-inflammatory cytokines IL-10 2.76, [1.88, 3.63]) TGF- β 3.89, [3.02, 4.76]). Additionally, reduced apoptosis levels −4.52, [−5.14, −3.89]), axonal regeneration markers NeuN cells/field 3.54, [2.65, 4.42]), NF200 4.88, [3.70, 6.05]), number Nissl bodies 1.89, [1.13, 2.65]), decreased astrogliosis marker GFAP −5.15, [−6.47, −3.82]). heterogeneity among primarily due variations transplantation doses, with increasing higher doses. Conclusion motor function by modulating inflammatory responses, reducing apoptosis, inhibiting astrogliosis, promoting regeneration. However, presence selection, performance, detection biases current may undermine evidence this study.

Language: Английский

Citations

2
Emerging Roles of Circular RNA in Macrophage Activation and Inflammatory Lung Responses DOI Creative Commons

Chang Jun Son,

Jonathan M. Carnino, Heedoo Lee

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(17), P. 1407 - 1407

Published: Aug. 23, 2024

Circular RNA (circRNA) is a type of single-stranded that forms covalently closed continuous loop, unlike linear RNA. The expression circRNAs in mammals often conserved across species and shows tissue cell specificity. Some circRNA serve as gene regulators. However, the biological function most unclear. CircRNA does not have 5' or 3' ends. unique structure provides them with much longer half-life more resistance to RNase R than RNAs. Inflammatory lung responses occur pathogenesis recovery many diseases. Macrophages form first line host defense/innate immune initiate/mediate inflammation. For example, bacterial pneumonia, upon pro-inflammatory activation, they release early response cytokines/chemokines recruit neutrophils, macrophages, lymphocytes sites infection clear pathogens. functional effects mechanisms by which exert physiological pathological roles macrophage activation inflammation remain poorly understood. In this article, we will review current understanding progress biogenesis, regulation, secretion, degradation. Furthermore, reports on role polarization, well process inflammatory responses.

Language: Английский

Citations

2
Extracellular vesicle therapy in neurological disorders DOI Creative Commons

Napasiri Putthanbut,

Jea-Young Lee, Cesar V. Borlongan

et al.

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: Aug. 25, 2024

Abstract Extracellular vesicles (EVs) are vital for cell-to-cell communication, transferring proteins, lipids, and nucleic acids in various physiological pathological processes. They play crucial roles immune modulation tissue regeneration but also involved pathogenic conditions like inflammation degenerative disorders. EVs have heterogeneous populations cargo, with numerous subpopulations currently under investigations. EV therapy shows promise stimulating repair serving as a drug delivery vehicle, offering advantages over cell therapy, such ease of engineering minimal risk tumorigenesis. However, challenges remain, including inconsistent nomenclature, complex characterization, underdeveloped large-scale production protocols. This review highlights the recent advances significance heterogeneity, emphasizing need better understanding their disease pathologies to develop tailored therapies clinical applications neurological Graphical abstract

Language: Английский

Citations

2
Research Progress on Treating Spinal Cord Injury by Modulating the Phenotype of Microglia DOI Creative Commons

Qinghe Yu,

Ziming Cai, Xiaofeng Liu

et al.

Journal of Integrative Neuroscience, Journal Year: 2024, Volume and Issue: 23(9)

Published: Sept. 19, 2024

Spinal cord injury (SCI) is a severe central nervous system disorder with no currently available effective treatment. Microglia are immune cells in the that play crucial roles SCI occurrence, development, and recovery stages. They exhibit dynamic polarization over time can switch between classical activation (M1) alternative (M2) phenotypes to respond environmental stimuli. The M1 phenotype involved initiating sustaining inflammatory responses, while M2 exerts anti-inflammatory effects promotes tissue repair damaged areas. Inhibiting promoting have become hotspots regulating neuroinflammation treating SCI. This article provides comprehensive review centered on modulating microglial for

Language: Английский

Citations

2