Association between neural stem/progenitor cells and biomaterials in spinal cord injury therapies: A systematic review and network meta-analysis.

Spinal cord injury (SCI) is associated with substantial healthcare challenges, frequently resulting in enduring sensory and motor deficits alongside various chronic complications. While advanced regenerative therapies have shown promise in preclinical research, their translation into clinical application has been limited. In response, this study utilized a comprehensive network meta-analysis to evaluate the effectiveness of neural stem/progenitor cell (NSPC) transplantation across animal models of SCI. We analyzed 363 outcomes from 55 distinct studies, categorizing the treatments into NSPCs alone (cell only), NSPCs with scaffolds (cell + scaffold), NSPCs with hydrogels (cell + hydrogel), standalone scaffolds (scaffold), standalone hydrogels (hydrogel), and control groups. Our analysis demonstrated significant enhancements in motor recovery, especially in gait function, within the NSPC treatment groups. Notably, the cell only group showed considerable improvements (standardized mean difference [SMD], 2.05; 95 % credible interval [CrI]: 1.08 to 3.10, p < 0.01), as did the cell + scaffold group (SMD, 3.73; 95 % CrI: 2.26 to 5.22, p < 0.001) and the cell + hydrogel group (SMD, 3.37; 95 % CrI: 1.02 to 5.78, p < 0.05) compared to controls. These therapeutic combinations not only reduced lesion cavity size but also enhanced neuronal regeneration, outperforming the cell only treatments. By integrating NSPCs with supportive biomaterials, our findings pave the way for refining these regenerative strategies to optimize their potential in clinical SCI treatment. Although there is no overall violation of consistency, the comparison of effect sizes between individual treatments should be interpreted in light of the inconsistency. STATEMENT OF SIGNIFICANCE: This study presents a comprehensive network meta-analysis exploring the efficacy of neural stem cell (NSC) transplantation, with and without biomaterials, in animal models of spinal cord injury (SCI). We demonstrate that NSCs, particularly when combined with biomaterials like scaffolds or hydrogels, significantly enhance motor and histological recovery post-SCI. These findings underscore the potential of NSC-based therapies, augmented with biomaterials, to advance SCI treatment, offering new insights into regenerative strategies that could significantly impact clinical practices.

Integrated Machine Learning Approach for the Early Prediction of Pressure Ulcers in Spinal Cord Injury Patients.

(1) Background: Pressure ulcers (PUs) substantially impact the quality of life of spinal cord injury (SCI) patients and require prompt intervention. This study used machine learning (ML) techniques to develop advanced predictive models for the occurrence of PUs in patients with SCI. (2) Methods: By analyzing the medical records of 539 patients with SCI, we observed a 35% incidence of PUs during hospitalization. Our analysis included 139 variables, including baseline characteristics, neurological status (International Standards for Neurological Classification of Spinal Cord Injury [ISNCSCI]), functional ability (Korean version of the Modified Barthel Index [K-MBI] and Functional Independence Measure [FIM]), and laboratory data. We used a variety of ML methods-a graph neural network (GNN), a deep neural network (DNN), a linear support vector machine (SVM_linear), a support vector machine with radial basis function kernel (SVM_RBF), K-nearest neighbors (KNN), a random forest (RF), and logistic regression (LR)-focusing on an integrative analysis of laboratory, neurological, and functional data. (3) Results: The SVM_linear algorithm using these composite data showed superior predictive ability (area under the receiver operating characteristic curve (AUC) = 0.904, accuracy = 0.944), as demonstrated by a 5-fold cross-validation. The critical discriminators of PU development were identified based on limb functional status and laboratory markers of inflammation. External validation highlighted the challenges of model generalization and provided a direction for future research. (4) Conclusions: Our study highlights the importance of a comprehensive, multidimensional data approach for the effective prediction of PUs in patients with SCI, especially in the acute and subacute phases. The proposed ML models show potential for the early detection and prevention of PUs, thus contributing substantially to improving patient care in clinical settings.

Electroceuticals for Regeneration of Long Nerve Gap Using Biodegradable Conductive Conduits and Implantable Wireless Stimulator.

Regeneration of over 10 mm long peripheral nerve defects remains a challenge due to the failure of regeneration by prolonged axotomy and denervation occurring in long-term recovery. Recent studies reveal that conductive conduits and electrical stimulation accelerate the regeneration of long nerve defects. In this study, an electroceutical platform combining a fully biodegradable conductive nerve conduit and a wireless electrical stimulator is proposed to maximize the therapeutic effect on nerve regeneration. Fully biodegradable nerve conduit fabricated using molybdenum (Mo) microparticles and polycaprolactone (PCL) can eliminate the unwanted effects of non-degradable implants, which occupy nerve paths and need to be removed through surgery increasing the risk of complications. The electrical and mechanical properties of Mo/PCL conduits are optimized by controlling the amounts of Mo and tetraglycol lubricant. The dissolution behavior and electrical conductivity of biodegradable nerve conduits in the biomimetic solutions are also evaluated. In in vivo experiments, the integrated strategy of a conductive Mo/PCL conduit with controlled therapeutic electrical stimulation shows accelerated axon regeneration for long sciatic nerve defects in rats compared to the use of the Mo/PCL conduit without stimulation and has a significant therapeutic effect based on the results obtained from the functional recovery test.

Delivery of Induced Neural Stem Cells Through Mechano-Tuned Silk-Collagen Hydrogels for the Recovery of Contused Spinal Cord in Rats.

Neural stem cells (NSC) have tremendous potential for therapeutic regeneration of diseased or traumatized neural tissues, including injured spinal cord. However, transplanted NSC suffer from low cell survival and uncontrolled differentiation, limiting in vivo efficacy. Here, this issue is tackled by delivery through silk-collagen protein hydrogels that are stiffness-matched, stress-relaxing, and shear-thinning. The mechanically-tuned hydrogels protect NSC reprogrammed from fibroblasts (iNSC) initially from injection shear-stress, and enhance long-term survival over 12 weeks. Hydrogel-iNSC treatment alleviates neural inflammation, with reduced inflammatory cells and lesions than NSC-only. The iNSC migrate from the hydrogel into surrounding tissues, secrete up-regulated neurotrophic factors, and differentiate into neural cell subtypes, forming synapses. More serotonergic axons are observed in the lesion cavity, and locomotor functions are improved in hydrogel-iNSC than in iNSC-only. This study highlights the ability of mechanically-tuned protein hydrogels to protect iNSC from the injection stress and severe inflammatory environment, allowing them to differentiate and function to recover the injured spinal cord.

Micropattern-based nerve guidance conduit with hundreds of microchannels and stem cell recruitment for nerve regeneration.

Guiding the regrowth of thousands of nerve fibers within a regeneration-friendly environment enhances the regeneration capacity in the case of peripheral nerve injury (PNI) and spinal cord injury (SCI). Although clinical treatments are available and several studies have been conducted, the development of nerve guidance conduits (NGCs) with desirable properties, including controllable size, hundreds of nerve bundle-sized microchannels, and host stem-cell recruitment, remains challenging. In this study, the micropattern-based fabrication method was combined with stem-cell recruitment factor (substance P, SP) immobilization onto the main material to produce a size-tunable NGC with hundreds of microchannels with stem-cell recruitment capability. The SP-immobilized multiple microchannels aligned the regrowth of nerve fibers and recruited the host stem cells, which enhanced the functional regeneration capacity. This method has wide applicability in the modification and augmentation of NGCs, such as bifurcated morphology or directional topographies on microchannels. Additional improvements in fabrication will advance the regeneration technology and improve the treatment of PNI/SCI.

Quantitative Analysis in Cervical Spinal Cord Injury Patients Using Diffusion Tensor Imaging and Tractography.

OBJECTIVE: To investigate the clinical usefulness of diffusion tensor imaging (DTI) and tractography in the prediction of outcomes after traumatic cervical spinal cord injury (SCI) and to assess whether the predictability is different between DTI and tractography administered before and after surgery. METHODS: Sixty-one subjects with traumatic cervical SCI were randomly assigned to preop or postop groups and received DTI accordingly. Among the patients who had DTI before surgery, we assigned 10 patients who had received repeated DTI examinations at 8 weeks after injury to the follow-up group. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained from DTI, and imaginary fiber and crossing fiber numbers were calculated from the tractography. Neurological status and functional status were assessed at 4 and 8 weeks after SCI. RESULTS: The neurologic and functional statuses of both groups improved after 4 weeks. Out of the initial 61 patients who were enrolled in the study, the failure rate of DTI image analysis was significantly higher in the postop group (n=17, 41.5%) than in the preop group (n=6, 20%). The FA values and fiber numbers in the preop group tended to be higher than those in the postop group, whereas ADC values were lower in the preop group. When comparing the tractographic findings in the follow-up group, imaginary fiber numbers at the C6 and C7 levels and crossing fiber numbers from the C3 to C6 levels were significantly decreased after surgery. Several DTI and tractographic parameters (especially the ADC value at the C4 level and imaginary fiber numbers at the C6 level) showed significant correlations with neurologic and functional statuses in both the preop and postop groups. These findings were most prominent when DTI and physical examination were simultaneously performed. CONCLUSION: Preoperative DTI and tractography demonstrated better FA and ADC values with lower interpretation failure rates than those obtained after surgery, whereas postoperative data significantly reflected the patient's clinical state at the time of evaluation. Therefore, DTI and tractography could be useful in predicting clinical outcomes after traumatic cervical SCI and should be interpreted separately before and after spine surgery.

The Time Sequence of Gene Expression Changes after Spinal Cord Injury.

Gene expression changes following spinal cord injury (SCI) are time-dependent, and an accurate understanding of these changes can be crucial in determining time-based treatment options in a clinical setting. We performed RNA sequencing of the contused spinal cord of rats at five different time points from the very acute to chronic stages (1 hour, 1 day, 1 week, 1 month, and 3 months) following SCI. We identified differentially expressed genes (DEGs) and Gene Ontology (GO) terms at each time point, and 14,257 genes were commonly expressed at all time points. The biological process of the inflammatory response was increased at 1 hour and 1 day, and the cellular component of the integral component of the synaptic membrane was increased at 1 day. DEGs associated with cell activation and the innate immune response were highly enriched at 1 week and 1 month, respectively. A total of 2841 DEGs were differentially expressed at any of the five time points, and 18 genes (17 upregulated and 1 downregulated) showed common expression differences at all time points. We found that interleukin signaling, neutrophil degranulation, eukaryotic translation, collagen degradation, LGI-ADAM interactions, GABA receptor, and L1CAM-ankyrin interactions were prominent after SCI depending on the time post injury. We also performed gene-drug network analysis and found several potential antagonists and agonists which can be used to treat SCI. We expect to discover effective treatments in the clinical field through further studies revealing the efficacy and safety of potential drugs.

Prediction of Poststroke Depression Based on the Outcomes of Machine Learning Algorithms.

Poststroke depression (PSD) is a major psychiatric disorder that develops after stroke; however, whether PSD treatment improves cognitive and functional impairments is not clearly understood. We reviewed data from 31 subjects with PSD and 34 age-matched controls without PSD; all subjects underwent neurological, cognitive, and functional assessments, including the National Institutes of Health Stroke Scale (NIHSS), the Korean version of the Mini-Mental Status Examination (K-MMSE), computerized neurocognitive test (CNT), the Korean version of the Modified Barthel Index (K-MBI), and functional independence measure (FIM) at admission to the rehabilitation unit in the subacute stage following stroke and 4 weeks after initial assessments. Machine learning methods, such as support vector machine, k-nearest neighbors, random forest, voting ensemble models, and statistical analysis using logistic regression were performed. PSD was successfully predicted using a support vector machine with a radial basis function kernel function (area under curve (AUC) = 0.711, accuracy = 0.700). PSD prognoses could be predicted using a support vector machine linear algorithm (AUC = 0.830, accuracy = 0.771). The statistical method did not have a better AUC than that of machine learning algorithms. We concluded that the occurrence and prognosis of PSD in stroke patients can be predicted effectively based on patients' cognitive and functional statuses using machine learning algorithms.

Self-assembling peptide gels promote angiogenesis and functional recovery after spinal cord injury in rats.

Spinal cord injury (SCI) leads to disruption of the blood-spinal cord barrier, hemorrhage, and tissue edema, which impair blood circulation and induce ischemia. Angiogenesis after SCI is an important step in the repair of damaged tissues, and the extent of angiogenesis strongly correlates with the neural regeneration. Various biomaterials have been developed to promote angiogenesis signaling pathways, and angiogenic self-assembling peptides are useful for producing diverse supramolecular structures with tunable functionality. RADA16 (Ac-RARADADARARADADA-NH2), which forms nanofiber networks under physiological conditions, is a self-assembling peptide that can provide mechanical support for tissue regeneration and reportedly has diverse roles in wound healing. In this study, we applied an injectable form of RADA16 with or without the neuropeptide substance P to the contused spinal cords of rats and examined angiogenesis within the damaged spinal cord and subsequent functional improvement. Histological and immunohistochemical analyses revealed that the inflammatory cell population in the lesion cavity was decreased, the vessel number and density around the damaged spinal cord were increased, and the levels of neurofilaments within the lesion cavity were increased in SCI rats that received RADA16 and RADA16 with substance P (rats in the RADA16/SP group). Moreover, real-time PCR analysis of damaged spinal cord tissues showed that IL-10 expression was increased and that locomotor function (as assessed by the Basso, Beattie, and Bresnahan (BBB) scale and the horizontal ladder test) was significantly improved in the RADA16/SP group compared to the control group. Our findings indicate that RADA16 modified with substance P effectively stimulates angiogenesis within the damaged spinal cord and is a candidate agent for promoting functional recovery post-SCI.

Enhanced Recognition of Amputated Wrist and Hand Movements by Deep Learning Method Using Multimodal Fusion of Electromyography and Electroencephalography.

Motion classification can be performed using biometric signals recorded by electroencephalography (EEG) or electromyography (EMG) with noninvasive surface electrodes for the control of prosthetic arms. However, current single-modal EEG and EMG based motion classification techniques are limited owing to the complexity and noise of EEG signals, and the electrode placement bias, and low-resolution of EMG signals. We herein propose a novel system of two-dimensional (2D) input image feature multimodal fusion based on an EEG/EMG-signal transfer learning (TL) paradigm for detection of hand movements in transforearm amputees. A feature extraction method in the frequency domain of the EEG and EMG signals was adopted to establish a 2D image. The input images were used for training on a model based on the convolutional neural network algorithm and TL, which requires 2D images as input data. For the purpose of data acquisition, five transforearm amputees and nine healthy controls were recruited. Compared with the conventional single-modal EEG signal trained models, the proposed multimodal fusion method significantly improved classification accuracy in both the control and patient groups. When the two signals were combined and used in the pretrained model for EEG TL, the classification accuracy increased by 4.18-4.35% in the control group, and by 2.51-3.00% in the patient group.

Prediction of Diabetic Sensorimotor Polyneuropathy Using Machine Learning Techniques.

Diabetic sensorimotor polyneuropathy (DSPN) is a major complication in patients with diabetes mellitus (DM), and early detection or prediction of DSPN is important for preventing or managing neuropathic pain and foot ulcer. Our aim is to delineate whether machine learning techniques are more useful than traditional statistical methods for predicting DSPN in DM patients. Four hundred seventy DM patients were classified into four groups (normal, possible, probable, and confirmed) based on clinical and electrophysiological findings of suspected DSPN. Three ML methods, XGBoost (XGB), support vector machine (SVM), and random forest (RF), and their combinations were used for analysis. RF showed the best area under the receiver operator characteristic curve (AUC, 0.8250) for differentiating between two categories-criteria by clinical findings (normal, possible, and probable groups) and those by electrophysiological findings (confirmed group)-and the result was superior to that of linear regression analysis (AUC = 0.6620). Average values of serum glucose, International Federation of Clinical Chemistry (IFCC), HbA1c, and albumin levels were identified as the four most important predictors of DSPN. In conclusion, machine learning techniques, especially RF, can predict DSPN in DM patients effectively, and electrophysiological analysis is important for identifying DSPN.

Predictors of Aspiration Pneumonia in the Elderly With Swallowing Dysfunction: Videofluoroscopic Swallowing Study.

OBJECTIVE: To identify the variables of videofluoroscopic swallowing study (VFSS) that are useful for predicting the risk of aspiration pneumonia in elderly patients with dysphagia. METHODS: A total of 251 patients (aged 65 years or more) were included and divided into a pneumonia group (n=133) and a non-pneumonia group (n=118). The pneumonia group included patients who had been diagnosed with aspiration pneumonia, and individuals in the non-pneumonia group did not have pneumonia but were referred for VFSS. The medical records and results of VFSS were reviewed and compared between the groups retrospectively. RESULTS: The pneumonia group exhibited a male preponderance and a higher 8-point Penetration-Aspiration Scale (8PPAS) score. The mean values of 8PPAS score for swallowing thick liquid and rice porridge was significantly higher in the pneumonia group. The pharyngeal delay time (PDT) and pharyngeal transit time (PTT) were significantly longer in the pneumonia group. The amounts of vallecular and pyriform sinus residue were increased in the pneumonia group. The delay in swallowing reflex and the decrease in laryngeal elevation were more frequently observed in the pneumonia group. Among those variables, PDT and PTT were identified as significant predictors of aspiration pneumonia based on logistic regression analysis. CONCLUSION: The present study delineated the findings of VFSS, suggesting an increased risk of aspiration pneumonia in elderly patients with dysphagia. The results demonstrate that prolonged PDT and PTT are significant predictors of aspiration pneumonia.

Effectiveness of Chin Tuck on Laryngeal Penetration: Quantitative Assessment.

The effectiveness of the chin tuck maneuver is still controversial, despite being widely used in clinical practice. The chin tuck maneuver has been shown to be able to reduce or eliminate aspiration in a group of patients with a number of favorable conditions, but its effectiveness in preventing or managing penetration remains unclear. This study was designed to investigate whether the chin tuck maneuver is effective in reducing penetration. Images from a videofluoroscopic swallowing study (VFSS) taken from 76 patients with penetration were collected and reviewed retrospectively. The severity of penetration was assessed by the penetration ratio (ratio of the penetration depth to the length of the epiglottis) measured and calculated from the images in which the deepest penetration was observed. The penetration ratio was significantly decreased in the chin tuck posture compared with the ratio in the neutral position (p = 0.001). Significant reducing effect was observed in 26 (34.2%) out of 76 patients. When comparing other parameters of VFSS, residues in the vallecular and pyriformis sinuses were less severe in the effective group. Chin tuck significantly decreased residues in both effective and ineffective group. The results demonstrate that the chin tuck maneuver can reduce penetration, but its effectiveness is limited.

Exercise Ameliorates Spinal Cord Injury by Changing DNA Methylation.

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.

Post-stroke Aphasia as a Prognostic Factor for Cognitive and Functional Changes in Patients With Stroke: Ischemic Versus Hemorrhagic.

OBJECTIVE: To investigate the comprehensive outcomes in aphasic patients, including their cognitive and functional status after ischemic or hemorrhagic stroke. It also aimed to clarify whether aphasia is a prognostic factor for cognitive and functional improvements in stroke patients. METHODS: Sixty-seven ischemic or hemorrhagic stroke patients in the subacute stage who had been diagnosed with aphasia using the Korean version of Frenchay Aphasia Screening Test (K-FAST) were included in the study. Forty-six stroke patients without aphasia were used as controls. All patients were examined with the Korean version of the Western Aphasia Battery (K-WAB). Cognitive and functional assessments of the patients including the Korean version of Mini-Mental State Examination (K-MMSE), and the Korean version of Modified Barthel Index (K-MBI) were performed during admission and 4 weeks after the initial assessments. RESULTS: The initial and follow-up total K-MMSE and K-MBI scores were significantly lower in aphasic patients than in non-aphasic controls. The K-WAB scores highly correlated with the total K-MMSE scores at the follow-up stage in all aphasic stroke patients. The K-WAB scores moderately correlated with the follow-up scores of the K-MBI in ischemic stroke patients but not in hemorrhagic stroke patients. CONCLUSION: Aphasia influences the cognitive and functional status of stroke patients and has a greater impact on cognitive improvement. Aphasia severity can be one of the prognostic factors for cognitive status in aphasic patients with stroke.

Ascorbic Acid Promotes Functional Restoration after Spinal Cord Injury Partly by Epigenetic Modulation.

Axonal regeneration after spinal cord injury (SCI) is difficult to achieve, and no fundamental treatment can be applied in clinical settings. DNA methylation has been suggested to play a role in regeneration capacity and neuronal growth after SCI by controlling the expression of regeneration-associated genes (RAGs). The aim of this study was to examine changes in neuronal DNA methylation status after SCI and to determine whether modulation of DNA methylation with ascorbic acid can enhance neuronal regeneration or functional restoration after SCI. Changes in epigenetic marks (5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC)); the expression of Ten-eleven translocation (Tet) family genes; and the expression of genes related to inflammation, regeneration, and degeneration in the brain motor cortex were determined following SCI. The 5hmC level within the brain was increased after SCI, especially in the acute and subacute stages, and the mRNA levels of Tet gene family members (Tet1, Tet2, and Tet3) were also increased. Administration of ascorbic acid (100 mg/kg) to SCI rats enhanced 5hmC levels; increased the expression of the Tet1, Tet2, and Tet3 genes within the brain motor cortex; promoted axonal sprouting within the lesion cavity of the spinal cord; and enhanced recovery of locomotor function until 12 weeks. In conclusion, we found that epigenetic status in the brain motor cortex is changed after SCI and that epigenetic modulation using ascorbic acid may contribute to functional recovery after SCI.

Decellularized brain matrix enhances macrophage polarization and functional improvements in rat spinal cord injury.

Spinal cord injury (SCI) is a devastating lesion lacking effective treatment options currently available in clinics. The inflammatory process exacerbates the extent of the lesion through a secondary injury mechanism, where proinflammatory classically activated macrophages (M1) are prevalent at the lesion site. However, the polarized alternatively activated anti-inflammatory macrophages (M2) are known to play an important role in wound healing and regeneration following SCI. Herein, we introduce porcine brain decellularized extracellular matrix (dECM) to modulate the macrophages in the injured spinal cord. The hydrogels with collagen and dECM at various dECM concentrations (1, 5, and 8 mg/ml) were used to cultivate primary macrophages and neurons. The dECM hydrogels were shown to promote the polarization of macrophages toward M2 phase and the neurite outgrowth of cortical and hippocampal neurons. When the dECM hydrogels were applied to rat SCI models, the proportion of M1 and M2 macrophages in the injured spinal cord was substantially altered. When received dECM concetration of 5 mg/ml, the expression of molecules associated with M2 (CD206, arginase1, and IL-10) was significantly increased. Consistently, the population of total macrophages and cavity area were substantially reduced in the dECM-treated groups. As a result, the locomotor functions of injured spinal cord, as assessed by BBB and ladder scoring, were significantly improved. Collectively, the porcine brain dECM with optimal concentration promotes functional recovery in SCI models through the activation of M2 macrophages, suggesting the promising use of the engineered hydrogels in the treatment of acute SCI. STATEMENT OF SIGNIFICANCE: Spinal cord injury (SCI) is a devastating lesion, lacking effective treatment options currently available in clinics. Here we delineated that the treatment of injured spinal cord with porcine brain decellularized matrix-based hydrogels for the first time, and could modulate the macrophage polarization and the ultimate functional recovery. When appropriate formulations were applied to a contused spinal cord model in rats, the decellularized matrix hydrogels shifted the macrophages to polarize to pro-regenerative M2 phenotype, decreased the size of lesion cavity, and finally promoted the locomotor functions until 8 weeks following the injury. We consider this work can significantly augment the matrix(biomaterial)-based therapeutic options, as an alternative to drug or cell-free approaches, for the treatment of acute injury of spinal cord.

Fusion of Reprogramming Factors Alters the Trajectory of Somatic Lineage Conversion.

Simultaneous expression of Oct4, Klf4, Sox2, and cMyc induces pluripotency in somatic cells (iPSCs). Replacing Oct4 with the neuro-specific factor Brn4 leads to transdifferentiation of fibroblasts into induced neural stem cells (iNSCs). However, Brn4 was recently found to induce transient acquisition of pluripotency before establishing the neural fate. We employed genetic lineage tracing and found that induction of iNSCs with individual vectors leads to direct lineage conversion. In contrast, polycistronic expression produces a Brn4-Klf4 fusion protein that enables induction of pluripotency. Our study demonstrates that a combination of pluripotency and tissue-specific factors allows direct somatic cell transdifferentiation, bypassing the acquisition of a pluripotent state. This result has major implications for lineage conversion technologies, which hold potential for providing a safer alternative to iPSCs for clinical application both in vitro and in vivo.

Repetitive Transcranial Magnetic Stimulation Enhances Recovery in Central Cord Syndrome Patients.

OBJECTIVE: To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on neurological and functional recovery in patients with central cord syndrome (CCS) involving the upper extremities between the treated and non-treated sides of the treated group and whether the outcomes are comparable to that of the untreated control group. METHODS: Nineteen CCS patients were treated with high-frequency (20 Hz) rTMS over the motor cortex for 5 days. The stimulation side was randomly selected, and all the subjects received conventional occupational therapy during the rTMS-treatment period. Twenty CCS patients who did not receive rTMS were considered as controls. Clinical assessments, including those by the International Standard for Neurological Classification of Spinal Cord Injury, the Jebsen-Taylor Hand Function Test, and the O'Connor Finger Dexterity Test were performed initially and followed up for 1 month after rTMS treatment or 5 weeks after initial assessments. RESULTS: The motor scores for upper extremities were increased and the number of improved cases was greater for the treated side in rTMS-treated patients than for the non-treated side in rTMS-treated patients or controls. The improved cases for writing time and score measured on the Jebsen-Taylor Hand Function Test were also significantly greater in number on the rTMS-treated side compared with the non-treated side and controls. There were no adverse effects during rTMS therapy or the follow-up period. CONCLUSION: The results of the application of high-frequency rTMS treatment to CCS patients suggest that rTMS can enhance the motor recovery and functional fine motor task performance of the upper extremities in such individuals.

Influence of Hip Fracture on Knee Pain During Postoperative Rehabilitation.

OBJECTIVE: To investigate whether fracture type, surgical procedure, or fracture grade affect knee pain during postoperative rehabilitation after a hip fracture. METHODS: We conducted a retrospective case-controlled study of 139 patients during postoperative rehabilitation after surgery for hip fractures. Patients were divided into two groups: patients experiencing knee pain during the first week of postoperative rehabilitation, and patients without knee pain. We compared the types of fracture, surgical procedure, and fracture grade between the two groups. RESULTS: We enrolled 52 patients (37.4%) with knee pain during the first weeks of postoperative rehabilitation. For type of fracture, knee pain was more common with intertrochanteric fracture than with femur neck fracture (48.8% vs. 21.1%, respectively; p=0.001). For the surgical procedure, there was no significant difference between the groups. For the fracture grade, the grades classified as unstable fractures were more common in the group of intertrochanteric fracture patients with knee pain than in those without knee pain (74.1% vs. 36.4%, respectively; p=0.002). CONCLUSION: Intertrochanteric fracture affected knee pain after hip fracture surgery more than did femur neck fracture, particularly in unstable fractures. Furthermore, there was no difference in each fracture type according to the surgical procedure. Careful examination and management for knee pain is needed in patients with hip fracture surgery.