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

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

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Biomaterial-based regenerative therapeutic strategies for spinal cord injury

NPG Asia Materials, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 19, 2024

Abstract As one of the most intractable neurological diseases, spinal cord injury (SCI) often leads to permanent impairment in patients. Unfortunately, due complex pathological mechanisms and unique postinjury microenvironment, there is currently no way completely repair injured cord. In recent years, with rapid development tissue engineering technology, combination biomaterials medicine has provided a new idea for treating SCI. Here, we systematically summarize representative biomaterials, including natural, synthetic, nano, hybrid materials, their applications SCI treatment. addition, describe several state-of-the-art fabrication techniques engineering. Importantly, provide novel insights use biomaterial-based therapeutic strategies reduce secondary damage promote repair. Finally, discuss biomaterial clinical studies. This review aims reference future exploration regeneration strategies.

Language: Английский

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M2 microglia-derived exosome-loaded electroconductive hydrogel for enhancing neurological recovery after spinal cord injury

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

Published: Jan. 3, 2024

Abstract Electroconductive hydrogels offer a promising avenue for enhancing the repair efficacy of spinal cord injuries (SCI) by restoring disrupted electrical signals along cord’s conduction pathway. Nonetheless, application composed diverse electroconductive materials has demonstrated limited capacity to mitigate post-SCI inflammatory response. Recent research indicated that transplantation M2 microglia effectively fosters SCI recovery attenuating excessive Exosomes (Exos), small vesicles discharged cells carrying similar biological functions their originating cells, present compelling alternative cellular transplantation. This investigation endeavors exploit microglia-derived exosomes (M2-Exos) successfully isolated and reversibly bonded through hydrogen bonding synergistic promotion synergistically enhance repair. In vitro experiments substantiated significant M2-Exos-laden stimulate growth neural stem axons in dorsal root ganglion modulate microglial polarization. Furthermore, M2-Exos remarkable ability initial reaction within injury site. When combined with hydrogel, worked expedite neuronal axonal regeneration, substantially functional rats afflicted SCI. These findings underscore potential as valuable reparative factor, amplifying foster rehabilitation.

Language: Английский

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Forsythoside B attenuates neuro-inflammation and neuronal apoptosis by inhibition of NF-κB and p38-MAPK signaling pathways through activating Nrf2 post spinal cord injury

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 111, P. 109120 - 109120

Published: Aug. 6, 2022

Language: Английский

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ROS-responsive nanoparticle delivery of ferroptosis inhibitor prodrug to facilitate mesenchymal stem cell-mediated spinal cord injury repair

Bioactive Materials, Journal Year: 2024, Volume and Issue: 38, P. 438 - 454

Published: May 12, 2024

Spinal cord injury (SCI) is a traumatic condition that results in impaired motor and sensory function. Ferroptosis one of the main causes neural cell death loss neurological function spinal cord, ferroptosis inhibitors are effective reducing inflammation repairing SCI. Although human umbilical mesenchymal stem cells (Huc-MSCs) can ameliorate inflammatory microenvironments promote regeneration SCI, their efficacy greatly limited by local microenvironment after Therefore, this study, we constructed drug-release nanoparticle system with synergistic Huc-MSCs inhibitor, which anchored Tz-A6 peptide based on CD44-targeting sequence, combined reactive oxygen species (ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at other end for SCI repair. Meanwhile, also modified classic inhibitor Ferrostatin-1 (Fer-1) synthesized new prodrug Feborastatin-1 (Feb-1). The showed treatment regimen significantly inhibited response promoted recovery rats This study developed combination therapy provides strategy construction drug-coordinated system.

Language: Английский

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Advances in the research of the role of macrophage/microglia polarization-mediated inflammatory response in spinal cord injury

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 1, 2022

It is often difficult to regain neurological function following spinal cord injury (SCI). Neuroinflammation thought be responsible for this failure. Regulating the inflammatory response post-SCI may contribute recovery of function. Over past few decades, studies have found that macrophages/microglia are one primary effector cells in SCI. Growing evidence has documented plastic can polarize microenvironmental signals into M1 and M2 macrophages/microglia. produces pro-inflammatory cytokines induce inflammation worsen tissue damage, while anti-inflammatory activities wound healing regeneration. Recent indicated transition from phenotype macrophage/microglia supports regression repair. Here, we will review role SCI In addition, discuss potential molecular mechanisms polarization, with emphasis on neuroprotective therapies modulate which provide new insights therapeutic strategies

Language: Английский

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Electroacupuncture Inhibits NLRP3 Activation by Regulating CMPK2 After Spinal Cord Injury

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 24, 2022

This study aimed to evaluate the expression of cytosine monophosphate kinase 2 (CMPK2) and activation NLRP3 inflammasome in rats with spinal cord injury (SCI) characterize effects electroacupuncture on CMPK2-associated regulation inflammasome.An SCI model was established Sprague-Dawley (SD) rats. The levels CMPK2 were measured at different time points following induction SCI. randomly divided into a sham group (Sham), (Model), an (EA), adeno-associated virus (AAV) group, AAV NC group. Electroacupuncture performed jiaji both sides T9 T11 for 20 min each day 3 consecutive days. In groups, viruses injected via microneedle using microscope stereotactic syringe. Basso-Beattie-Bresnahan (BBB) score used motor function Histopathological changes tissue detected H&E staining, NLRP3, CMPK2, ASC, caspase-1, IL-18, IL-1β quantified Western blotting (WB), immunofluorescence (IF), RT-PCR.The cords significantly increased 1 compared those (p < 0.05). decreased gradually over remained low 14 days post-SCI. We successfully constructed showed that knocked down dilutions. Finally, treatment EA or resulted BBB scores histomorphology groups than groups. WB, IF, PCR analyses lower 0.05).Our regulated Activation is critical mechanism inflammatory response downregulated inhibited which could improve

Language: Английский

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Mode of action of astrocytes in pain: From the spinal cord to the brain

Progress in Neurobiology, Journal Year: 2022, Volume and Issue: 219, P. 102365 - 102365

Published: Oct. 10, 2022

Language: Английский

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Multipotent Mesenchymal Stem Cell-Based Therapies for Spinal Cord Injury: Current Progress and Future Prospects

Biology, Journal Year: 2023, Volume and Issue: 12(5), P. 653 - 653

Published: April 26, 2023

Spinal cord injury (SCI) represents a significant medical challenge, often resulting in permanent disability and severely impacting the quality of life for affected individuals. Traditional treatment options remain limited, underscoring need novel therapeutic approaches. In recent years, multipotent mesenchymal stem cells (MSCs) have emerged as promising candidate SCI due to their multifaceted regenerative capabilities. This comprehensive review synthesizes current understanding molecular mechanisms underlying MSC-mediated tissue repair SCI. Key discussed include neuroprotection through secretion growth factors cytokines, promotion neuronal regeneration via MSC differentiation into neural cell types, angiogenesis release pro-angiogenic factors, immunomodulation by modulating immune activity, axonal driven neurotrophic glial scar reduction modulation extracellular matrix components. Additionally, examines various clinical applications MSCs treatment, such direct transplantation injured spinal cord, engineering using biomaterial scaffolds that support survival integration, innovative cell-based therapies like MSC-derived exosomes, which possess neuroprotective properties. As field progresses, it is crucial address challenges associated with MSC-based therapies, including determining optimal sources, intervention timing, delivery methods, well developing standardized protocols isolation, expansion, characterization. Overcoming these will facilitate translation preclinical findings practice, providing new hope improved individuals living devastating consequences

Language: Английский

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The dual role of microglia in neuropathic pain after spinal cord injury: Detrimental and protective effects

Experimental Neurology, Journal Year: 2023, Volume and Issue: 370, P. 114570 - 114570

Published: Oct. 16, 2023

Language: Английский

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