IPSC-NSCs-derived exosomal let-7b-5p improves motor function after spinal cord Injury by modulating microglial/macrophage pyroptosis DOI Creative Commons
Jie Liu,

Guang Kong,

Chenlin Lu

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 9, 2024

Abstract Background Following spinal cord injury (SCI), the inflammatory storm initiated by microglia/macrophages poses a significant impediment to recovery process. Exosomes play crucial role in transport of miRNAs, facilitating essential cellular communication through transfer genetic material. However, miRNAs from iPSC-NSCs-Exos and their potential mechanisms leading repair after SCI remain unclear. This study aims explore microglia/macrophage pyroptosis reveal mechanisms. Methods were characterized identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), Western blot. A mouse model series vivo vitro experiments conducted investigate therapeutic effects iPSC-NSCs-Exos. Subsequently, miRNA microarray rescue performed confirm SCI. Mechanistic studies carried out blot, luciferase activity assays, RNA-ChIP. Results Our findings revealed that iPSC-NSCs-derived exosomes inhibited at 7 days post-SCI, maintaining myelin integrity promoting axonal growth, ultimately improving mice motor function. The showed let-7b-5p be highly enriched iPSC-NSCs-Exos, LRIG3 was as target gene let-7b-5p. Through experiments, we uncovered connection between iPSC-NSCs microglia/macrophages, revealing novel for treating Conclusion In conclusion, discovered can package deliver let-7b-5p, regulating expression ameliorate enhance function highlights combined therapy with functional limiting inflammation following

Language: Английский

Spinal cord injury: molecular mechanisms and therapeutic interventions DOI Creative Commons
Xiao Hu, Wei Xu, Yilong Ren

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 26, 2023

Abstract Spinal cord injury (SCI) remains a severe condition with an extremely high disability rate. The challenges of SCI repair include its complex pathological mechanisms and the difficulties neural regeneration in central nervous system. In past few decades, researchers have attempted to completely elucidate mechanism identify effective strategies promote axon circuit remodeling, but results not been ideal. Recently, new SCI, especially interactions between immune cell responses, revealed by single-cell sequencing spatial transcriptome analysis. With development bioactive materials stem cells, more attention has focused on forming intermediate networks reconstruction than promoting axonal corticospinal tract. Furthermore, technologies control physical parameters such as electricity, magnetism ultrasound constantly innovated applied fate regulation. Among these advanced novel technologies, therapy, biomaterial transplantation, electromagnetic stimulation entered into stage clinical trials, some them already treatment. this review, we outline overall epidemiology pathophysiology expound latest research progress related detail, propose future directions for applications.

Language: Английский

Citations

311
Astrocytes in human central nervous system diseases: a frontier for new therapies DOI Creative Commons
Alexei Verkhratsky, Arthur M. Butt, Baoman Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 13, 2023

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence the central nervous system (CNS). contribute pathophysiology all neurological neuropsychiatric disorders in ways that can be either beneficial or detrimental disorder outcome. Pathophysiological changes astroglia primary secondary result gain loss functions. respond external, non-cell autonomous signals associated with any form CNS pathology by undergoing complex variable their structure, molecular expression, function. In addition, internally driven, cell astroglial innate properties lead pathologies. Astroglial is complex, different pathophysiological states phenotypes context-specific vary disorder, disorder-stage, comorbidities, age, sex. Here, we classify into (i) reactive astrogliosis, (ii) atrophy function, (iii) degeneration death, (iv) astrocytopathies characterised aberrant forms drive disease. We review across spectrum human diseases disorders, including neurotrauma, stroke, neuroinfection, autoimmune attack epilepsy, as well neurodevelopmental, neurodegenerative, metabolic disorders. Characterising cellular mechanisms represents new frontier identify novel therapeutic strategies.

Language: Английский

Citations

171
Microglia regulation of central nervous system myelin health and regeneration DOI
Sarah Kent, Véronique E. Miron

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 24(1), P. 49 - 63

Published: July 14, 2023

Language: Английский

Citations

71
Mesenchymal stem cells in the treatment of spinal cord injury: Mechanisms, current advances and future challenges DOI Creative Commons

Yuanliang Xia,

Jianshu Zhu,

Ruohan Yang

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 24, 2023

Spinal cord injury (SCI) has considerable impact on patient physical, mental, and financial health. Secondary SCI is associated with inflammation, vascular destruction, subsequent permanent damage to the nervous system. Mesenchymal stem cells (MSCs) have anti-inflammatory properties, promoting regeneration release neuro-nutrients, are a promising strategy for treatment of SCI. Preclinical studies shown that MSCs promote sensory motor function recovery in rats. In clinical trials, been reported improve American Injury Association (ASIA) scores. However, effectiveness treating patients remains controversial. tumorigenesis ensuring survival hostile environment challenging. this article we examine evidence pathophysiological changes occurring after We then review underlying mechanisms summarize potential application practice. Finally, highlight challenges surrounding use discuss future applications.

Language: Английский

Citations

54
Alpinetin inhibits neuroinflammation and neuronal apoptosis via targeting the JAK2/STAT3 signaling pathway in spinal cord injury DOI Creative Commons
Shining Xiao, Yu Zhang, Zihao Liu

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(4), P. 1094 - 1108

Published: Jan. 10, 2023

Abstract Background A growing body of research shows that drug monomers from traditional Chinese herbal medicines have antineuroinflammatory and neuroprotective effects can significantly improve the recovery motor function after spinal cord injury (SCI). Here, we explore role molecular mechanisms Alpinetin on activating microglia‐mediated neuroinflammation neuronal apoptosis SCI. Methods Stimulation microglia with lipopolysaccharide (LPS) to simulate models in vitro, effect release pro‐inflammatory mediators LPS‐induced its mechanism were detected. In addition, a co‐culture system cells was constructed assess apoptosis. Finally, rat used study inflammation, apoptosis, axonal regeneration, Alpinetin. Results inhibits activity JAK2/STAT3 pathway. also reverse activated reactive oxygen species (ROS) production decrease mitochondrial membrane potential (MMP) PC12 cells. vivo inflammatory response improves function. Conclusion be treat neurodegenerative diseases is novel candidate for treatment neuroinflammation.

Language: Английский

Citations

49
Fate mapping of Spp1 expression reveals age-dependent plasticity of disease-associated microglia-like cells after brain injury DOI Creative Commons

Yangning Lan,

Xiaoxuan Zhang, Shaorui Liu

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(2), P. 349 - 363.e9

Published: Feb. 1, 2024

Language: Английский

Citations

34
Temporal single-cell atlas of non-neuronal retinal cells reveals dynamic, coordinated multicellular responses to central nervous system injury DOI
Inbal Benhar, Jiarui Ding, Wenjun Yan

et al.

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(4), P. 700 - 713

Published: Feb. 20, 2023

Language: Английский

Citations

33
An In Vitro and Ex Vivo Analysis of the Potential of GelMA Hydrogels as a Therapeutic Platform for Preclinical Spinal Cord Injury DOI Creative Commons
Ciara M. Walsh, Jacek K. Wychowaniec,

Louise Costello

et al.

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(26)

Published: April 28, 2023

Abstract Spinal cord injury (SCI) is a devastating condition with no curative therapy currently available. Immunomodulation can be applied as therapeutic strategy to drive alternative immune cell activation and promote proregenerative microenvironment. Locally injected hydrogels carrying immunotherapeutic cargo directly injured tissue offer an encouraging treatment approach from immunopharmacological perspective. Gelatin methacrylate (GelMA) are promising in this regard, however, detailed analysis on the immunogenicity of GelMA specific context SCI microenvironment lacking. Here, formulated translationally relevant photoinitiator analyzed vitro ex vivo. 3% ( w/v ) GelMA, synthesized gelatin type‐A, first identified optimal hydrogel formulation based mechanical properties cytocompatibility. Additionally, GelMA‐A does not alter expression profile key polarization markers BV2 microglia or RAW264.7 macrophages after 48 h. Finally, it shown for time that support vivo culture primary murine organotypic spinal slices 14 days direct effect glial fibrillary acidic protein (GFAP + astrocyte ionized calcium‐binding adaptor molecule 1 (Iba‐1 reactivity. This provides evidence act hydrogel‐based platform preclinical SCI.

Language: Английский

Citations

29
Age-dependent immune and lymphatic responses after spinal cord injury DOI Creative Commons
Andrea Francesca Salvador, Taitea Dykstra, Justin Rustenhoven

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(14), P. 2155 - 2169.e9

Published: May 5, 2023

Language: Английский

Citations

27
Synergistic effects of tetramethylpyrazine and astragaloside IV on spinal cord injury via alteration of astrocyte A1/A2 polarization through the Sirt1-NF-κB pathway DOI
Yaojian Rao, Junjie Li,

Ruofei Qiao

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 131, P. 111686 - 111686

Published: March 10, 2024

Language: Английский

Citations

13