Spinal cord injury: molecular mechanisms and therapeutic interventions

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

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Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury

Cell stem cell, Journal Year: 2020, Volume and Issue: 27(3), P. 430 - 440.e5

Published: Aug. 5, 2020

Language: Английский

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Current Advancements in Spinal Cord Injury Research—Glial Scar Formation and Neural Regeneration

Cells, Journal Year: 2023, Volume and Issue: 12(6), P. 853 - 853

Published: March 9, 2023

Spinal cord injury (SCI) is a complex tissue resulting in permanent and degenerating damage to the central nervous system (CNS). Detrimental cellular processes occur after SCI, including axonal degeneration, neuronal loss, neuroinflammation, reactive gliosis, scar formation. The glial border forms segregate neural lesion isolate spreading inflammation, oxygen species, excitotoxicity at epicenter preserve surrounding healthy tissue. physicochemical barrier composed of elongated astrocytes, fibroblasts, microglia secreting chondroitin sulfate proteoglycans, collogen, dense extra-cellular matrix. While this physiological response preserves viable tissue, it also detrimental regeneration. To overcome negative outcomes associated with formation, therapeutic strategies have been developed: prevention resolution developed scar, cell transplantation into lesion, endogenous reprogramming. This review focuses on cellular/molecular aspects discusses advantages disadvantages promote regeneration SCI.

Language: Английский

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Hypoxia-stimulated mesenchymal stem cell-derived exosomes loaded by adhesive hydrogel for effective angiogenic treatment of spinal cord injury

Biomaterials Science, Journal Year: 2022, Volume and Issue: 10(7), P. 1803 - 1811

Published: Jan. 1, 2022

Due to the limited efficacy of current clinical treatment strategies, functional recovery after traumatic spinal cord injury (SCI) remains a knotty problem be solved. Apart from anti-inflammation and cell replenishing treatments, accumulating evidence implies that promoting angiogenesis would also potentially benefit tissue regeneration SCI. In this research, inspired by role exosomes in cell-cell communication exosomal alteration resulting cells under stress, were engineered through hypoxia stimulation mesenchymal stem proposed as an alternative for SCI therapy. Hypoxia-stimulated (hypo-Exo) transplanted into injured via encapsulation peptide-modified adhesive hydrogel pro-angiogenic therapy The peptide PPFLMLLKGSTR-modified hyaluronic acid replenished cavity caused achieved local delivery exosomes. hypoxia-inducible factor 1-alpha content hypo-Exo was significantly increased, overexpression vascular endothelial growth surrounding transplant system. Ultimately, prominent demonstrated both vitro vivo, indicating immense potential hydrogel-encapsulated treating central nervous system trauma other ischemia diseases.

Language: Английский

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Porous microneedle patch with sustained delivery of extracellular vesicles mitigates severe spinal cord injury

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 7, 2023

Abstract The transplantation of mesenchymal stem cells-derived secretome, particularly extracellular vesicles is a promising therapy to suppress spinal cord injury-triggered neuroinflammation. However, efficient delivery the injured cord, with minimal damage, remains challenge. Here we present device for treat injury. We show that incorporating cells and porous microneedles enables vesicles. demonstrate topical application lesion beneath dura, does not damage lesion. evaluate efficacy our in contusive injury model find it reduces cavity scar tissue formation, promotes angiogenesis, improves survival nearby tissues axons. Importantly, sustained at least 7 days results significant functional recovery. Thus, provides an platform treatment.

Language: Английский

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Supramolecular Hydrogel Microspheres of Platelet-Derived Growth Factor Mimetic Peptide Promote Recovery from Spinal Cord Injury

ACS Nano, Journal Year: 2023, Volume and Issue: 17(4), P. 3818 - 3837

Published: Feb. 14, 2023

Neural stem cells (NSCs) are considered to be prospective replacements for neuronal cell loss as a result of spinal cord injury (SCI). However, the survival and differentiation NSCs strongly affected by unfavorable microenvironment induced SCI, which critically impairs their therapeutic ability treat SCI. Herein, strategy fabricate PDGF-MP hydrogel (PDGF-MPH) microspheres (PDGF-MPHM) instead bulk hydrogels is proposed dramatically enhance efficiency platelet-derived growth factor mimetic peptide (PDGF-MP) in activating its receptor. PDGF-MPHM were fabricated piezoelectric ceramic-driven thermal electrospray device, had an average size 9 μm, also activate PDGFRβ more effectively than PDGF-MPH. In vitro, exerted strong neuroprotective effects maintaining proliferation inhibiting apoptosis presence myelin extracts. vivo, inhibited M1 macrophage infiltration extrinsic or intrinsic on seventh day after Eight weeks T10 SCI treatment results showed that + significantly promoted differentiation, reduced lesion size, considerably improved motor function recovery rats stimulating axonal regeneration, synapse formation, angiogenesis comparison with graft group. Therefore, our findings provide insights into promising agent repair.

Language: Английский

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3D bio-printed living nerve-like fibers refine the ecological niche for long-distance spinal cord injury regeneration

Bioactive Materials, Journal Year: 2023, Volume and Issue: 25, P. 160 - 175

Published: Feb. 2, 2023

3D bioprinting holds great promise toward fabricating biomimetic living constructs in a bottom-up assembly manner. To date, various emergences of have been bioprinted for

Language: Английский

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Stem Cell Therapy for Spinal Cord Injury

Cell Transplantation, Journal Year: 2021, Volume and Issue: 30

Published: Jan. 1, 2021

Traumatic spinal cord injury (SCI) results in direct and indirect damage to neural tissues, which motor sensory dysfunction, dystonia, pathological reflex that ultimately lead paraplegia or tetraplegia. A loss of cells, axon regeneration failure, time-sensitive pathophysiology make tissue repair difficult. Despite various medical developments, there are currently no effective regenerative treatments. Stem cell therapy is a promising treatment for SCI due its multiple targets reactivity benefits. The present review focuses on stem therapy, including bone marrow mesenchymal umbilical adipose-derived progenitor embryonic induced pluripotent extracellular vesicles. Each type certain features pathology shows therapeutic effects via replacement, nutritional support, scaffolds, immunomodulation mechanisms. However, many preclinical studies growing number clinical trials found single-cell treatments had only limited benefits SCI. multifaceted, consensus combined needed.

Language: Английский

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Cell-adaptable dynamic hydrogel reinforced with stem cells improves the functional repair of spinal cord injury by alleviating neuroinflammation

Biomaterials, Journal Year: 2021, Volume and Issue: 279, P. 121190 - 121190

Published: Oct. 21, 2021

Spinal cord injury (SCI) is one of the most challenging clinical issues. It characterized by disruption neural circuitry and connectivity, resulting in neurological disability. Adipose-derived stem cells (ADSCs) serve as a promising source therapeutic for SCI treatment. However, outcomes direct ADSCs transplantation are limited presence an inflammatory microenvironment. Herein, cell-adaptable neurogenic (CaNeu) hydrogel was developed delivery vehicle to promote neuronal regeneration after SCI. The dynamic network CaNeu loaded with provides cell-infiltratable matrix that enhances axonal growth eventually leads improved motor evoked potential, hindlimb strength, coordination complete spinal transection rats. Furthermore, also establishes anti-inflammatory microenvironment inducing shift polarization recruited macrophages toward pro-regeneration (M2) phenotype. Our study showed CaNeu-hydrogel‒mediated resulted significantly suppressed neuroinflammation apoptosis, this phenomenon involved PI3K/Akt signaling pathway. findings indicate valuable assist cell therapy SCI, providing strategy central nervous system diseases.

Language: Английский

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Advances in Biomaterial‐Based Spinal Cord Injury Repair

Advanced Functional Materials, Journal Year: 2021, Volume and Issue: 32(13)

Published: Dec. 1, 2021

Abstract Spinal cord injury (SCI) often leads to the loss of motor and sensory functions is a major challenge in neurological clinical practice. Understanding pathophysiological changes inhibitory microenvironment crucial enable identification potential mechanisms for functional restoration provide guidance development efficient treatment repair strategies. To date, implantation specifically functionalized biomaterials lesion area has been shown help promote axon regeneration facilitate neuronal circuit generation by remolding SCI microenvironments. Moreover, structural spinal through transplantation naive tissue grafts from adult donors, artificial cord‐like developed engineering, 3D printing will open up new avenues treatment. This review focuses on dynamic microenvironments, repairs, strategies restoring structure function, experimental animal models, regenerative mechanisms, studies repair. The current status, recent advances, challenges, prospects scaffold‐based basic settings are summarized discussed, reference that guide future exploration

Language: Английский

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