Therapy For Spinal Cord Injury Research Articles

P.144 Comparative analysis of spinal cord-derived and induced pluripotent-derived neural stem & progenitor cells for SCI therapy

Background: Induced pluripotent stem cells (iPSCs) have revolutionized spinal cord injury (SCI) treatment by generating neural stem/progenitor cells (NSPCs). However, understanding how iPSC-derived NSPCs compare to authentic spinal cord NSPCs remains unclear. This study thoroughly characterizes bona fide spinal cord NSPCs and their isogenic iPSC-derived counterparts, iPSC-SC and iPSC-Br. Methods: Human spinal cord and skin tissue were obtained with ethics approval to establish primary NSPC cultures. iPSCs were derived from these primary cells and differentiated into iPSC-SC and iPSC-Br NSPCs. Assessments encompassed differentiation, proliferation capabilities, immunostaining, and RNA sequencing for differential gene expression. Results: Functional and transcriptional differences were identified between bona fide NSPCs and iPSC-SC/iPSC-Br. Bona fide and iPSC-SC NSPCs exhibited spinal cord regionalization, while iPSC-Br displayed forebrain regionalization. iPSC-derived NSPCs shared features reminiscent of early developmental stages, including embryonic patterning genes and increased proliferation rates. Notably, differentiation profiles were most similar between bona fide and iPSC-Br, with substantial distinctions observed between bona fide and iPSC-SC. Conclusions: This study unveils unique regional, developmental, and functional characteristics distinguishing spinal cord NSPCs from iPSC-derived counterparts. Addressing these disparities holds promise for enhancing iPSC-derived NSPC therapies in spinal cord injuries, contributing to a deeper understanding of their potential applications in regenerative medicine.

Advancements in neuroregenerative and neuroprotective therapies for traumatic spinal cord injury

Traumatic spinal cord injuries (SCIs) continue to be a major healthcare concern, with a rising prevalence worldwide. In response to this growing medical challenge, considerable scientific attention has been devoted to developing neuroprotective and neuroregenerative strategies aimed at improving the prognosis and quality of life for individuals with SCIs. This comprehensive review aims to provide an up-to-date and thorough overview of the latest neuroregenerative and neuroprotective therapies currently under investigation. These strategies encompass a multifaceted approach that include neuropharmacological interventions, cell-based therapies, and other promising strategies such as biomaterial scaffolds and neuro-modulation therapies. In addition, the review discusses the importance of acute clinical management, including the role of hemodynamic management as well as timing and technical aspects of surgery as key factors mitigating the secondary injury following SCI. In conclusion, this review underscores the ongoing scientific efforts to enhance patient outcomes and quality of life, focusing on upcoming strategies for the management of traumatic SCI. Each section provides a working knowledge of the fundamental preclinical and patient trials relevant to clinicians while underscoring the pathophysiologic rationale for the therapies.

Crosstalk Between Cell Death and Spinal Cord Injury: Neurology and Therapy.

Spinal cord injury (SCI) often leads to neurological dysfunction, and neuronal cell death is one of the main causes of neurological dysfunction. After SCI, in addition to necrosis, programmed cell death (PCD) occurs in nerve cells. At first, studies recognized only necrosis, apoptosis, and autophagy. In recent years, researchers have identified new forms of PCD, including pyroptosis, necroptosis, ferroptosis, and cuproptosis. Related studies have confirmed that all of these cell death modes are involved in various phases of SCI and affect the direction of the disease through different mechanisms and pathways. Furthermore, regulating neuronal cell death after SCI through various means has been proven to be beneficial for the recovery of neural function. In recent years, emerging therapies for SCI have also provided new potential methods to restore neural function. Thus, the relationship between SCI and cell death plays an important role in the occurrence and development of SCI. This review summarizes and generalizes the relevant research results on neuronal necrosis, apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis after SCI to provide a new understanding of neuronal cell death after SCI and to aid in the treatment of SCI.

A New Paradigm in Spinal Cord Injury Therapy: from Cell-free Treatment to Engineering Modifications.

Spinal cord injury (SCI) is an intractable and poorly prognostic neurological disease, and current treatments are still unable to cure it completely and avoid sequelae. Extracellular vesicles (EVs), as important carriers of intercellular communication and pharmacological effects, are considered to be the most promising candidates for SCI therapy because of their low toxicity and immunogenicity, their ability to encapsulate endogenous bioactive molecules (e.g., proteins, lipids, and nucleic acids), and their ability to cross the blood-brain/cerebrospinal barriers. However, poor targeting, low retention rate, and limited therapeutic efficacy of natural EVs have bottlenecked EVs-based SCI therapy. A new paradigm for SCI treatment will be provided by engineering modified EVs. Furthermore, our limited understanding of the role of EVs in SCI pathology hinders the rational design of novel EVbased therapeutic approaches. In this study, we review the pathophysiology after SCI, especially the multicellular EVs-mediated crosstalk; briefly describe the shift from cellular to cell-free therapies for SCI treatment; discuss and analyze the issues related to the route and dose of EVs administration; summarize and present the common strategies for EVs drug loading in the treatment of SCI and point out the shortcomings of these drug loading methods; finally, we analyze and highlight the feasibility and advantages of bio-scaffold-encapsulated EVs for SCI treatment, providing scalable insights into cell-free therapy for SCI.

Screening strategy identified idebenone loaded ROS-responsive nano-polyphenolic vesicle for spinal cord injury therapy

Spinal cord injury (SCI) is a severe central nerve diseases which lacks effective of treatment. Oxidative stress is a major pathological factor for SCI. It may induce mitochondrial damage, which further lead to ferroptosis and apoptosis in neural cells during SCI. Thus, targeting oxidative stress may be the key strategy for SCI treatment. In this study, we carried out screening experiment in the natural product library against oxidative stress in neural cells. It was identified that idebenone (IDE) may potently suppress oxidative stress induced cell death in neural cells. Furthermore, we successfully developed a multifunctional nanovesicles, which we named IDE@PPNs, by encapsulating IDE within proanthocyanidin polyphenol nanovesicles (PPNs). IDE@PPNs exhibited lysosomal escape capability and mitochondrial ROS responsiveness; meanwhile, they may suppress ferroptosis and apoptosis in neural cells. In vivo study demonstrated that IDE@PPNs may promote motor function recovery in rats and suppress ferroptosis and apoptosis in neurons. It may also show high biocompatibility in in vivo study. In summary, we fabricated a novel natural product loaded ROS responsive nanovesicles, IDE@PPNs may have the great potential for SCI therapy.

Long-Term Mouse Spinal Cord Organotypic Slice Culture as a Platform for Validating Cell Transplantation in Spinal Cord Injury.

Resolutive cures for spinal cord injuries (SCIs) are still lacking, due to the complex pathophysiology. One of the most promising regenerative approaches is based on stem cell transplantation to replace lost tissue and promote functional recovery. This approach should be further explored better in vitro and ex vivo for safety and efficacy before proceeding with more expensive and time-consuming animal testing. In this work, we show the establishment of a long-term platform based on mouse spinal cord (SC) organotypic slices transplanted with human neural stem cells to test cellular replacement therapies for SCIs. Standard SC organotypic cultures are maintained for around 2 or 3 weeks in vitro. Here, we describe an optimized protocol for long-term maintenance (≥30 days) for up to 90 days. The medium used for long-term culturing of SC slices was also optimized for transplanting neural stem cells into the organotypic model. Human SC-derived neuroepithelial stem (h-SC-NES) cells carrying a green fluorescent protein (GFP) reporter were transplanted into mouse SC slices. Thirty days after the transplant, cells still show GFP expression and a low apoptotic rate, suggesting that the optimized environment sustained their survival and integration inside the tissue. This protocol represents a robust reference for efficiently testing cell replacement therapies in the SC tissue. This platform will allow researchers to perform an ex vivo pre-screening of different cell transplantation therapies, helping them to choose the most appropriate strategy before proceeding with in vivo experiments.

Sustained delivery of NT-3 and curcumin augments microenvironment modulation effects of decellularized spinal cord matrix hydrogel for spinal cord injury repair.

Decellularized extracellular matrix hydrogel, especially that derived from spinal cord (DSCM hydrogel), has been actively considered as a functional biomaterial for remodeling the extracellular matrix of the native tissue, due to its unique characteristics in constructing pro-regenerative microenvironment for neural stem cells (NSCs). Furthermore, DSCM hydrogel can provide multiple binding domains to growth factors and drugs. Therefore, both exogenous neurotrophic factors and anti-inflammatory drugs are highly desired to be incorporated into DSCM hydrogel, which may synergistically modulate the complex microenvironment at the lesion site after spinal cord injury (SCI). Herein, neurotrophin-3 (NT-3) and curcumin (Cur) were integrated into DSCM hydrogel for SCI therapy. Due to different affinities to the DSCM hydrogel, NT-3 underwent a controlled release manner, while curcumin released explosively within the first 24 h, followed by rather sustained but slower release. The integration of both NT-3 and curcumin significantly enhanced NSCs proliferation and their neuronal differentiation. Meanwhile, the release of curcumin promoted macrophages polarization into anti-inflammatory subtypes, which further facilitated NSCs differentiation into neurons. The in situ injected DSCM + NT3 + Cur hydrogel exerted superior capability in alleviating the inflammatory responses in rat contused spinal cord. Compared to DSCM hydrogel alone, DSCM + NT3 + Cur hydrogel more significantly promoted the recruitment of NSCs and their neuronal differentiation at the lesion site. These outcomes favored functional recovery, as evidenced by the improved hind limb movement. Overall, the bioactive DSCM hydrogel can serve as a multifunctional carrier for cooperatively release of growth factors and drugs, which significantly benefits microenvironment regulation and nerve regeneration after SCI.

Constructing Linear-Oriented Pre-Vascularized Human Spinal Cord Tissues for Spinal Cord Injury Repair.

Repairing spinal cord injury (SCI) is a global medical challenge lacking effective clinical treatment. Developing human-engineered spinal cord tissues that can replenish lost cells and restore a regenerative microenvironment offers promising potential for SCI therapy. However, creating vascularized human spinal cord-like tissues (VSCT) that mimic the diverse cell types and longitudinal parallel structural features of spinal cord tissues remains a significant hurdle. In the present study, VSCTs are engineered using embryonic human spinal cord-derived neural and endothelial cells on linear-ordered collagen scaffolds (LOCS). Studies have shown that astrocytes and endothelial cells align along the scaffolds in VSCT, supporting axon extension from various human neurons myelinated by oligodendrocytes. After transplantation into SCI rats, VSCT survives at the injury sites and promotes endogenous neural regeneration and vascularization, ultimately reducing scarring and enhancing behavioral functional recovery. It suggests that pre-vascularization of engineered spinal cord tissues is beneficial for SCI treatment and highlights the important role of exogenous endothelial cells in tissue engineering.

Metabolic reprogramming: a new option for the treatment of spinal cord injury

Abstract Spinal cord injuries impose a notably economic burden on society, mainly because of the severe after effects they cause. Despite the ongoing development of various therapies for spinal cord injuries, their effectiveness remains unsatisfactory. However, a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming. In this review, we explore the metabolic changes that occur during spinal cord injuries, their consequences, and the therapeutic tools available for metabolic reprogramming. Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling. However, spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism, lipid metabolism, and mitochondrial dysfunction. These metabolic disturbances lead to corresponding pathological changes, including the failure of axonal regeneration, the accumulation of scarring, and the activation of microglia. To rescue spinal cord injury at the metabolic level, potential metabolic reprogramming approaches have emerged, including replenishing metabolic substrates, reconstituting metabolic couplings, and targeting mitochondrial therapies to alter cell fate. The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury. To further advance the metabolic treatment of the spinal cord injury, future efforts should focus on a deeper understanding of neurometabolism, the development of more advanced metabolomics technologies, and the design of highly effective metabolic interventions.

Neuroprotective Effects of Coenzyme Q10 and Ozone Therapy on Experimental Traumatic Spinal Cord Injuries in Rats

This study investigates the neuroprotective effects and functional recovery potential of Coenzyme Q10 (CoQ10) and ozone therapy in spinal cord injury (SCI). In this study, 40 female Sprague-Dawley rats were divided into five groups of eight. Surgical procedures induced spinal cord trauma in all groups, except the control group. The ozone group received 0.7 mg/kg rectal ozone daily for seven days, starting one hour post-spinal cord trauma. The CoQ10 group was administered 120 mg/kg CoQ10 orally once daily for seven days, beginning 24 hours prior to trauma. The CoQ10 + ozone group received both treatments. Examinations included a modified Tarlov scale and inclined plane test on days 1, 3, 5, and 7. Malondialdehyde (MDA) analysis was conducted on serum samples, and assessments of caspase-3, Bcl-2, and Bax levels were performed on tissue samples. Additionally, a comprehensive examination analyzed histopathological and ultrastructural changes. After SCI, there was a statistically significant increase in serum MDA, tissue caspase-3, and Bax levels (MDA p<0.001, caspase-3 p<0.001, Bax p=0.003). In the CoQ10 + ozone group, serum MDA (p=0.002), tissue caspase-3 (p=0.001), and Bax (p=0.030) levels were significantly lower compared to the trauma group. Tissue Bcl-2 levels were also significantly higher (p=0.019). The combined treatment group demonstrated improved histopathological, ultrastructural, and neurological outcomes. This study shows that CoQ10 + ozone therapy in traumatic SCI demonstrates neuroprotective effects via antioxidant and antiapoptotic mechanisms. The positive effects on functional recovery are supported by data from biochemical, histopathological, ultrastructural, and neurological examinations.

Identification of hub genes and key pathways in spinal cord injury via bioinformatics analysis.

This study aimed to explore the hub genes and related key pathways in Spinal Cord Injury (SCI) based on the bioinformatics analysis. Two microarray datasets (GSE45006, GSE45550) were obtained from the GEO database and were merged and batch-corrected. The differentially expressed genes (DEGs) in SCI were explored with the Limma, and the weighted gene co-expression network analysis (WGCNA) was conducted to explore the module genes. Functional enrichment analysis and Gene set variation analysis (GSVA) were used to investigate the biological functions and key pathways of the key genes related to SCI. Then the protein-protein interaction (PPI) network was generated using the STING online tool, and the hub genes in SCI were identified. Receiver operating characteristic (ROC) curves were applied to assess the diagnostic value of the selected hub genes. We identified 554 DEGs in SCI, and 1236 key genes in SCI were selected via WGCNA. Totally 111 key genes related to SCI were discovered. Furthermore, the functional enrichment analysis showed that these key mRNAs were primarily enriched in the extracellular matrix (ECM)-related pathways and processes associated with wound healing and cell growth. The PPI network further filtered six hub genes (Cd44, Timp1, Loxl1, Col6a1, Col3a1, Col5a1) ranked by the degree, and the diagnostic value of the six hub genes was confirmed by the ROC curves. Six hub genes including Cd44, Timp1, Loxl1, Col6a1, Col3a1, and Col5a1 were identified in SCI, with differential expression and excellent diagnostic value, which might provide insight into the targeted therapy of SCI.

Necroptosis pathway emerged as potential diagnosis markers in spinal cord injury.

The present research focused on identifying necroptosis-related differentially expressed genes (NRDEGs) in spinal cord injury (SCI) to highlight potential therapeutic and prognostic target genes in clinical SCI. Three SCI-related datasets were downloaded, including GSE151371, GSE5296 and GSE47681. MSigDB and KEGG datasets were searched for necroptosis-related genes (NRGs). Differentially expressed genes (DEGs) and NRGs were intersected to obtain NRDEGs. The MCC algorithm was employed to select the first 10 genes as hub genes. A protein-protein interaction (PPI) network related to NRDEGs was developed utilizing STRING. Several databases were searched to predict interactions between hub genes and miRNAs, transcription factors, potential drugs, and small molecules. Immunoassays were performed to identify DEGs using CIBERSORTx. Additionally, qRT-PCR was carried out to verify NRDEGs in an animal model of SCI. Combined analysis of all datasets identified 15 co-expressed DEGs and NRGs. GO and KEGG pathway analyses highlighted DEGs mostly belonged to pathways associated with necroptosis and apoptosis. Hub gene expression analysis showed high accuracy in SCI diagnosis was associated with the expression of CHMP7 and FADD. A total of two hub genes, i.e. CHMP7, FADD, were considered potential targets for SCI therapy.

Current status and future perspectives on stem cell transplantation for spinal cord injury.

Previous assessments of stem cell therapy for spinal cord injuries (SCI) have encountered challenges and constraints. Current research primarily emphasizes safety in early-phase clinical trials, while systematic reviews prioritize effectiveness, often overlooking safety and translational feasibility. This situation prompts inquiries regarding the readiness for clinical adoption. To offer an up-to-date systematic literature review of clinical trial results con cerning stem cell therapy for SCI. A systematic search was conducted across major medical databases [PubMed, Embase, Reference Citation Analysis (RCA), and Cochrane Library] up to October 14, 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "spinal cord", "injury", "clinical trials", "stem cells", "functional outcomes", and "adverse events". Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of SCI. In a comprehensive review of 66 studies on stem cell therapies for SCI, 496 papers were initially identified, with 237 chosen for full-text analysis. Among them, 236 were deemed eligible after excluding 170 for various reasons. These studies encompassed 1086 patients with varying SCI levels, with cervical injuries being the most common (42.2%). Bone marrow stem cells were the predominant stem cell type used (71.1%), with various administration methods. Follow-up durations averaged around 84.4 months. The 32.7% of patients showed functional impro vement from American spinal injury association Impairment Scale (AIS) A to B, 40.8% from AIS A to C, 5.3% from AIS A to D, and 2.1% from AIS B to C. Sensory improvements were observed in 30.9% of patients. A relatively small number of adverse events were recorded, including fever (15.1%), headaches (4.3%), muscle tension (3.1%), and dizziness (2.6%), highlighting the potential for SCI recovery with stem cell therapy. In the realm of SCI treatment, stem cell-based therapies show promise, but clinical trials reveal potential adverse events and limitations, underscoring the need for meticulous optimization of transplantation conditions and parameters, caution against swift clinical implementation, a deeper understanding of SCI pathophysiology, and addressing ethical, tumorigenicity, immunogenicity, and immunotoxicity concerns before gradual and careful adoption in clinical practice.

Astrogliosis: A review of the astrocytic mechanisms, imaging modes, and treatments in spinal cord injury patients

Astrocytes are cells in the central nervous system (CNS) that are responsible for many things, such as maintaining blood brain barrier (BBB), regulating synapses in the spinal cord, and responding to spinal cord injury (SCI). Astrogliosis, the astrocytic response to spinal cord injuries (SCIs), helps repair CNS damages by regulating different protein filaments, thus limiting axonal growth. Former studies that were demonstrated through laser capture microdissection and immunohistochemistry (IHC) helped to identify important genes involved in experimental therapies for SCIs. Additionally, there are potential clinical treatments options for SCIs such as hydrogels, mesenchymal stem cells and steroids. Increased imaging modalities indicate that excessive astrogliosis can have adverse effects. These imaging techniques include positron emission tomography (PET), magnetic resonance imaging (MRI), and two-photon laser-scanning microscopy (TPLSM). These techniques illuminate greater details of the astrocytic response to SCIs. Despite these findings, astrogliosis is not well understood by the research community. Many of the studies presented in this literature review are experimental attempts to understand the mechanisms of astrogliosis in SCIs. This literature review aims to summarize the methods of each study in visualizing the mechanisms of astrogliosis and how they play a role in SCIs. Furthermore, this paper is aimed to comprehensively bridge the developments in the treatment for SCI patients based on innovative imaging modalities. Compared to prior studies, this review utilizes more recent understandings of the astrogliosis mechanisms to highlight insights into targeted developments, both clinically and preclinically. Some limitations of this literature review include the limited studies on astrogliosis and its impact on SCIs. Nonetheless, there is ongoing potential in the search for treatments for SCIs.

Recent advances in implantable 3D-printed scaffolds for repair of spinal cord injury

Spinal cord injury (SCI) is an important factor in sensory and motor disorders that affects thousands of people every year. Currently, despite successes in basic science and clinical research, there are few effective methods in the treatment of chronic and acute spinal cord injuries. In the last decade, the use of 3D printed scaffolds in the treatment of SCI had satisfactory and promising results. By providing a microenvironment around the injury site and in combination with growth factors or cells, 3D printed scaffolds help in axon regeneration as well as neural recovery after SCI. Here, we provide an overview of tissue engineering, 3D printing scaffolds, the different polymers used and their characterization methods. This review highlights the recent encouraging applications of 3D printing scaffolds in developing the novel SCI therapy.

Interleukin-4 from curcumin-activated OECs emerges as a central modulator for increasing M2 polarization of microglia/macrophage in OEC anti-inflammatory activity for functional repair of spinal cord injury

Microglia/macrophages are major contributors to neuroinflammation in the central nervous system (CNS) injury and exhibit either pro- or anti-inflammatory phenotypes in response to specific microenvironmental signals. Our latest in vivo and in vitro studies demonstrated that curcumin-treated olfactory ensheathing cells (aOECs) can effectively enhance neural survival and axonal outgrowth, and transplantation of aOECs improves the neurological outcome after spinal cord injury (SCI). The therapeutic effect is largely attributed to aOEC anti-inflammatory activity through the modulation of microglial polarization from the M1 to M2 phenotype. However, very little is known about what viable molecules from aOECs are actively responsible for the switch of M1 to M2 microglial phenotypes and the underlying mechanisms of microglial polarization. Herein, we show that Interleukin-4 (IL-4) plays a leading role in triggering the M1 to M2 microglial phenotype, appreciably decreasing the levels of M1 markers IL‑1β, IL‑6, tumour necrosis factor-alpha (TNF-α) and inducible nitric oxide synthase (iNOS) and elevating the levels of M2 markers Arg-1, TGF-β, IL-10, and CD206. Strikingly, blockade of IL-4 signaling by siRNA and a neutralizing antibody in aOEC medium reverses the transition of M1 to M2, and the activated microglia stimulated with the aOEC medium lacking IL-4 significantly decreases neuronal survival and neurite outgrowth. In addition, transplantation of aOECs improved the neurological function deficits after SCI in rats. More importantly, the crosstalk between JAK1/STAT1/3/6-targeted downstream signals and NF-κB/SOCS1/3 signaling predominantly orchestrates IL-4-modulated microglial polarization event. These results provide new insights into the molecular mechanisms of aOECs driving the M1-to-M2 shift of microglia and shed light on new therapies for SCI through the modulation of microglial polarization.

Transplantation of Neural Stem Cells Loaded in an IGF-1 Bioactive Supramolecular Nanofiber Hydrogel for the Effective Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) leads to massive cell death, disruption, and demyelination of axons, resulting in permanent motor and sensory dysfunctions. Stem cell transplantation is a promising therapy for SCI. However, owing to the poor microenvironment that develops following SCI, the bioactivities of these grafted stem cells are limited. Cell implantation combined with biomaterial therapies is widely studied for the development of tissue engineering technology. Herein, an insulin-like growth factor-1 (IGF-1)-bioactive supramolecular nanofiber hydrogel (IGF-1 gel) is synthesized that can activate IGF-1 downstream signaling, prevent the apoptosis of neural stem cells (NSCs), improve their proliferation, and induce their differentiation into neurons and oligodendrocytes. Moreover, implantation of NSCs carried out with IGF-1 gels promotes neurite outgrowth and myelin sheath regeneration at lesion sites following SCI. In addition, IGF-1 gels can enrich extracellular vesicles (EVs) derived from NSCs or from nerve cells differentiated from these NSCs via miRNAs related to axonal regeneration and remyelination, even in an inflammatory environment. These EVs are taken up by autologous endogenous NSCs and regulate their differentiation. This study provides adequate evidence that combined treatment with NSCs and IGF-1 gels is a potential therapeutic strategy for treating SCI.

Exploring the Landscape of Hydrogel Therapy for Spinal Cord Injury: A Bibliometric and Visual Analysis (1991–2023)

BackgroundThis study aimed to conduct a bibliometric analysis of the literature on hydrogel therapy for spinal cord injury to visualize the research status, identify hotspots, and explore the development trends in this field. MethodsWeb of science Core Collection database was searched for relevant studies published between January 1991 and December 2023. Data such as journal title, author information, institutional affiliation, country, citation and keywords were extracted. Bibliometrix, CiteSpace and VOSviewer were used to perform bibliometric analysis of the retrieved data. ResultsA total of 1099 articles pertaining to hydrogel therapy for spinal cord injury were retrieved, revealing an upward trajectory in both annual publication volume and cumulative publication volume. Biomaterials emerged as the journal with the highest number of publications and the most rapid cumulative publication growth, contributing 84 articles. Among authors, Shoichet MS stood out with the highest number of publications and citations, totaling 66 articles. The University of Toronto led in institutional contributions with 65 publications, while China dominated in country-specific publications, accounting for 374 articles.However, to foster significant academic achievements, it is imperative for diverse authors, institutions, and countries to enhance collaboration. Current research in this field concentrates on scaffold architecture, nerve growth factor, the fibrotic microenvironment, and guidance channels. Simultaneously, upcoming research directions prioritize 3D bioprinting, injectable hydrogel, inflammation, and nanoparticles within the realm of hydrogel therapy for spinal cord injuries. ConclusionIn summary, this study provided a comprehensive analysis of the current research status and frontiers of hydrogel therapy for spinal cord injury. The findings provide a foundation for future research and clinical translation efforts of hydrogel therapy in this field.

Unravelling the Road to Recovery: Mechanisms of Wnt Signalling in Spinal Cord Injury.

Spinal cord injury (SCI) is a complex neurodegenerative pathology that consistently harbours a poor prognostic outcome. At present, there are few therapeutic strategies that can halt neuronal cell death and facilitate functional motor recovery. However, recent studies have highlighted the Wnt pathway as a key promoter of axon regeneration following central nervous system (CNS) injuries. Emerging evidence also suggests that the temporal dysregulation of Wnt may drive cell death post-SCI. A major challenge in SCI treatment resides in developing therapeutics that can effectively target inflammation and facilitate glial scar repair. Before Wnt signalling is exploited for SCI therapy, further research is needed to clarify the implications of Wnt on neuroinflammation during chronic stages of injury. In this review, an attempt is made to dissect the impact of canonical and non-canonical Wnt pathways in relation to individual aspects of glial and fibrotic scar formation. Furthermore, it is also highlighted how modulating Wnt activity at chronic time points may aid in limiting lesion expansion and promoting axonal repair.

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

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