The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity

Military Medical Research, Journal Year: 2022, Volume and Issue: 9(1)

Published: Nov. 19, 2022

Abstract Bone, cartilage, and soft tissue regeneration is a complex spatiotemporal process recruiting variety of cell types, whose activity interplay must be precisely mediated for effective healing post-injury. Although extensive strides have been made in the understanding immune microenvironment processes governing bone, regeneration, clinical translation these mechanisms remains challenge. Regulation increasingly becoming favorable target regeneration; therefore, an in-depth communication between cells functional would valuable. Herein, we review regulatory role promotion maintenance stem states context repair regeneration. We discuss roles various subsets introduce novel strategies, example, biomaterial-targeting activity, aimed at regulating healing. Understanding crosstalk pathways may shed light on new therapeutic opportunities enhancing through regulation microenvironment.

Language: Английский

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Immune response following traumatic spinal cord injury: Pathophysiology and therapies

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 6, 2023

Traumatic spinal cord injury (SCI) is a devastating condition that often associated with significant loss of function and/or permanent disability. The pathophysiology SCI complex and occurs in two phases. First, the mechanical damage from trauma causes immediate acute cell dysfunction death. Then, secondary mechanisms further propagate death over course days, weeks, or even months. Among mechanisms, inflammation has been shown to be key determinant severity significantly worsens functional outcomes. Thus, addition surgical management SCI, selectively targeting immune response following could substantially decrease progression improve patient In order develop such therapies, detailed molecular understanding timing necessary. Recently, several studies have mapped cytokine/chemokine proliferation patterns SCI. this review, we examine underlying assess both current future therapies including pharmaceutical stem therapy, exciting potential extracellular vesicle therapy.

Language: Английский

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Neuronal Redevelopment and the Regeneration of Neuromodulatory Axons in the Adult Mammalian Central Nervous System

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: April 22, 2022

One reason that many central nervous system injuries, including those arising from traumatic brain injury, spinal cord and stroke, have limited recovery of function is neurons within the adult mammalian CNS lack ability to regenerate their axons following trauma. This stands in contrast peripheral (PNS). New evidence, provided by single-cell expression profiling, suggests that, both can revert an embryonic-like growth state which permissive for axon regeneration. "redevelopment" strategy could facilitate a damage response necessary isolate repair acute injury provide intracellular machinery regrowth. Interestingly, serotonin rostral group raphe nuclei, project into forebrain, display robust unaided, counter widely held view cannot without experimental intervention after injury. Furthermore, initial evidence norepinephrine locus coeruleus possess similar regenerative abilities. Several morphological characteristics regeneration mammals, observable using longitudinal vivo imaging, are distinct known unaided nerve regeneration, or seen optic occurs with intervention. These results suggest there alternative program likely differs displayed PNS.

Language: Английский

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Therapeutic Potential of Mesenchymal Stem Cells (MSCs) and MSC-Derived Extracellular Vesicles for the Treatment of Spinal Cord Injury

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(24), P. 13672 - 13672

Published: Dec. 20, 2021

Spinal cord injury (SCI) is a life-threatening condition that leads to permanent disability with partial or complete loss of motor, sensory, and autonomic functions. SCI usually caused by initial mechanical insult, followed cascade several neuroinflammation structural changes. For ameliorating the neuroinflammatory cascades, MSC has been regarded as therapeutic agent. The animal research demonstrated can be valuable agent growth factors cytokines may induce anti-inflammatory regenerative effects. However, efficacy MSCs in models inconsistent, optimal method remains debatable. Moreover, there are limitations developing these agents for humans. Therefore, identifying novel medicine necessary. Extracellular vesicles source medicine; they possess nucleic acids, functional proteins, bioactive lipids perform various functions, including damaged tissue repair, immune response regulation, reduction inflammation. MSC-derived exosomes have advantages over MSCs, small dimensions, low immunogenicity, no need additional procedures culture expansion delivery. Certain studies extracellular (EVs), exosomes, exhibit outstanding chondroprotective we reviewed principles patho-mechanisms summarized outcomes EVs SCI, reported date.

Language: Английский

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The roles and applications of neural stem cells in spinal cord injury repair

Frontiers in Bioengineering and Biotechnology, Journal Year: 2022, Volume and Issue: 10

Published: Aug. 29, 2022

Spinal cord injury (SCI), which has no current cure, places a severe burden on patients. Stem cell-based therapies are considered promising in attempts to repair injured spinal cords; such options include neural stem cells (NSCs). NSCs multipotent that differentiate into neuronal and neuroglial lineages. This feature makes suitable candidates for regenerating cords. Many studies have revealed the therapeutic potential of NSCs. In this review, we discuss from an integrated view how can help SCI repair. We will sources NSCs, as well representative pre-clinical clinical trials NSC-based

Language: Английский

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Mesenchymal Stem Cell Therapy in Traumatic Spinal Cord Injury: A Systematic Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11719 - 11719

Published: July 20, 2023

Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of central nervous system restore cells, myelin, and neural connections. Cell therapy, particularly with mesenchymal stem cells (MSCs), holds significant promise for TSCI treatment. This systematic review aims analyze efficacy, safety, therapeutic potential MSC-based cell therapies in TSCI. A comprehensive search PUBMED COCHRANE databases until February 2023 was conducted, combining terms such as “spinal injury,” “stem cells,” therapy,” “mesenchymal “traumatic injury”. Among 53 studies initially identified, 22 (21 clinical trials 1 case series) were included. Findings these consistently demonstrate improvements AIS (ASIA Impairment Scale) grades, sensory scores, and, lesser extent, motor scores. Meta-analyses further support positive outcomes. have shown short- medium-term indicated by absence adverse events within studied timeframe. However, caution required when drawing generalized recommendations scientific evidence available. Further research needed elucidate long-term safety implications advancements. Although progress has been made, therapies, additional exploring other future gene neurostimulation techniques, tissue engineering approaches are essential understanding evolving treatment landscape.

Language: Английский

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Macrophage–Neuroglia Interactions in Promoting Neuronal Regeneration in Zebrafish

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6483 - 6483

Published: March 30, 2023

The human nervous system exhibits limited regenerative capabilities following damage to the central (CNS), leading a scarcity of effective treatments for nerve function recovery. In contrast, zebrafish demonstrate remarkable abilities, making them an ideal model studying modulation inflammatory processes after injury. Such research holds significant translational potential enhance our understanding recovery from and disease. Macrophages play crucial role in tissue repair regeneration, with their subpopulations indirectly promoting axonal regeneration through developmental signals. AP-1 signaling pathway, mediated by TNF/Tnfrsf1a, can elevate HDAC1 expression facilitate regeneration. Furthermore, spinal cord injury (SCI), pMN progenitors have been observed switch between oligodendrocyte motor neuron fates, macrophage-secreted TNF-α potentially regulating differentiation ependymal–radial glia oligodendrocytes. Radial glial cells (RGs) are also essential CNS zebrafish, as they perform neurogenesis gliogenesis, specific RG existing generation neurons This review article underscores critical macrophages focusing on secretion TNF-α, which promotes zebrafish. We offer insights into molecular mechanisms underlying TNF-α’s ability explore progenitor RGs SCI concludes discussion various unresolved questions field, ideas suggested future research. Studying innate immune cell interactions neuroglia may lead development novel strategies treating associated medicine, commonly

Language: Английский

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Regenerative medicine strategies for chronic complete spinal cord injury

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(4), P. 818 - 824

Published: Sept. 4, 2023

Spinal cord injury is a condition in which the parenchyma of spinal damaged by trauma or various diseases. While rapid progress has been made regenerative medicine for that was previously untreatable, most research this field focused on early phase incomplete injury. However, majority patients have chronic severe injuries; therefore, treatments these situations are fundamental importance. The reason why treatment complete not studied that, unlike stage injury, there inhibitors neural regeneration. Thus, we assumed it difficult to address all conditions with single and combination several essential target pathologies. First, established therapy cell transplantation drug-releasing scaffolds, contributes functional recovery after transection but found limited still needs further investigation. Here, development review necessary approaches different pathologies based our findings many studies accumulated date discuss, reference literature, effective achieving recovery.

Language: Английский

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Design and synthesis of nano-biomaterials based on graphene and local delivery of cerebrolysin into the injured spinal cord of mice, promising neural restoration

Nanoscale Advances, Journal Year: 2024, Volume and Issue: 6(3), P. 990 - 1000

Published: Jan. 1, 2024

Spinal cord injury (SCI) is an incurable and catastrophic health issue with no clinical solution. As part of cascade reactions, the inflammatory process fibrous glial scar production aggravate amount lesion through a secondary damage mechanism, encouraging scientists from other disciplines to investigate new paths for solving this problem. Graphene oxide (GO) its derivatives are among most promising biomedical nerve tissue regeneration materials due their remarkable chemical, mechanical, electrical properties. This paper designs introduces GO-based nanomaterial minimize inflammation stimulate neurite regrowth. To improve biocompatibility, biodegradability, cell proliferation, GO plates were modified polyethylene glycol (PEG) Au nanoparticles as neuroprotective antibacterial agents, respectively. Preliminary biological investigations on bone marrow derived mesenchymal stem cells (BM-MSCs) various concentrations graphenic nanocarrier indicated lack toxicity enhancement in BM-MSC proliferation about 10% after 48 hours. Therapeutic nanostructures used T10 segment mouse SCI model. The pathological immunohistochemical data revealed that refilling cavities, decreasing degeneration, establishing neuroregeneration resulted considerable improvement hind limb motor function. Furthermore, compared nanocomposite mixture alone, intraspinal delivery cerebrolysin (CRL) had more satisfying impact regrowth, cystic cavity, hemorrhage avoidance, function enhancement. study demonstrates potential nanomaterials treatment applications.

Language: Английский

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Epigenetic regulation and factors that influence the effect of iPSCs-derived neural stem/progenitor cells (NS/PCs) in the treatment of spinal cord injury

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: Feb. 21, 2024

Abstract Spinal cord injury (SCI) is a severe neurological disorder that causes impairment and disability. Neural stem/progenitor cells (NS/PCs) derived from induced pluripotent stem (iPSCs) represent promising cell therapy strategy for spinal regeneration repair. However, iPSC-derived NS/PCs face many challenges issues in SCI therapy; one of the most significant epigenetic regulation factors influence this mechanism. Epigenetics refers to gene expression function by DNA methylation, histone modification, chromatin structure without changing sequence. Previous research has shown epigenetics plays crucial role generation, differentiation, transplantation iPSCs, can quality, safety, outcome transplanted cells. In study, we review effects various influencing on at multiple levels, including reprogramming, regulation, adaptation iPSCs during transplantation, as well impact other therapeutic tools (e.g., drugs, electrical stimulation, scaffolds) status We summarize our main findings insights field identify future directions need be addressed explored.

Language: Английский

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