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Spinal cord injury (SCI) causes axonal damage and demyelination, neural cell death, and comprehensive tissue loss, resulting in devastating neurological dysfunction. Neural stem/progenitor cell (NSPCs) transplantation provides therapeutic benefits for neural repair in SCI, and glial cell line-derived neurotrophic factor (GDNF) has been uncovered to have capability of stimulating axonal regeneration and remyelination after SCI. In this study, to evaluate whether GDNF would augment therapeutic effects of NSPCs for SCI, GDNF-encoding or mock adenoviral vector-transduced human NSPCs (GDNF-or Mock-hNSPCs) were transplanted into the injured thoracic spinal cords of rats at 7 days after SCI. Grafted GDNF-hNSPCs showed robust engraftment, long-term survival, an extensive distribution, and increased differentiation into neurons and oligodendroglial cells. Compared with Mock-hNSPC- and vehicle-injected groups, transplantation of GDNF-hNSPCs significantly reduced lesion volume and glial scar formation, promoted neurite outgrowth, axonal regeneration and myelination, increased Schwann cell migration that contributed to the myelin repair, and improved locomotor recovery. In addition, tract tracing demonstrated that transplantation of GDNF-hNSPCs reduced significantly axonal dieback of the dorsal corticospinal tract (dCST), and increased the levels of dCST collaterals, propriospinal neurons (PSNs), and contacts between dCST collaterals and PSNs in the cervical enlargement over that of the controls. Finally grafted GDNF-hNSPCs substantially reversed the increased expression of voltage-gated sodium channels and neuropeptide Y, and elevated expression of GABA in the injured spinal cord, which are involved in the attenuation of neuropathic pain after SCI. These findings suggest that implantation of GDNF-hNSPCs enhances therapeutic efficiency of hNSPCs-based cell therapy for SCI.

Gene therapy technologies are inevitably required to boost the therapeutic performance of cell therapies; thus, validating the efficacy of gene carriers specifically used for preparing cellular therapeutics is a prerequisite for evaluating the therapeutic capabilities of gene and cell combinatorial therapies. Herein, the efficacy of a recombinant adeno-associated virus derivative (rAAVr3.45) was examined to evaluate its potential as a gene carrier for genetically manipulating interleukin-10 (IL10)-secreting human neural stem cells (hNSCs) that can potentially treat ischemic injuries or neurological disorders. Safety issues that could arise during the virus preparation or viral infection were investigated; no replication-competent AAVs were detected in the final cell suspensions, transgene expression was mostly transient, and no severe interference on endogenous gene expression by viral infection occurred. IL10 secretion from hNSCs infected by rAAVr3.45 encoding IL10 did not alter the transcriptional profile of any gene by more than threefold, but the exogenously boosted IL10 was sufficient to provoke immunomodulatory effects in an ischemic brain injury animal model, thereby accelerating the recovery of neurological deficits and the reduction of brain infarction volume. This study presents evidence that rAAVr3.45 can be potentially used as a gene carrier to prepare stem cell therapeutics.

Neural progenitor cells (NPCs) therapy offers great promise in hypoxic-ischemic (HI) brain injury. However, the poor survival of implanted NPCs in the HI host environment limits their therapeutic effects. Tumor necrosis factor-alpha (TNF-&alpha, ) is a pleiotropic cytokine that is induced in response to a variety of pathological processes including inflammation and immunity. On the other hand, TNF-&alpha, has protective effects on cell apoptosis and death and affects the differentiation, proliferation, and survival of neural stem/progenitor cells in the brain. The present study investigated whether TNF-&alpha, pretreatment on human NPCs (hNPCs) enhances the effectiveness of cell transplantation therapy under ischemic brain. Fetal brain tissue-derived hNPCs were pretreated with TNF-&alpha, before being used in vitro experiments or transplantation. TNF-&alpha, significantly increased expression of cIAP2, and the use of short hairpin RNA-mediated knockdown of cIAP2 demonstrated that cIAP2 protected hNPCs against HI-induced cytotoxicity. In addition, pretreatment of hNPCs with TNF-&alpha, mediated neuroprotection by altering microglia polarization via increased expression of CX3CL1 and by enhancing expression of neurotrophic factors. Furthermore, transplantation of TNF-&alpha, treated hNPCs reduced infarct volume and improved neurological functions in comparison with non-pretreated hNPCs or vehicle. These findings show that TNF-&alpha, pretreatment, which protects hNPCs from HI-injured brain-induced apoptosis and increases neuroprotection, is a simple and safe approach to improve the survival of transplanted hNPCs and the therapeutic efficacy of hNPCs in HI brain injury.

Concrete is the most widely used construction material, and huge amounts of natural resources are required to manufacture it. With relatively recent rapid industrial development as well as the improvement of people’s living standards, the volume of domestic and industrial waste is increasing, and much of this waste is not recycled. Cathode ray tube (CRT) waste glass is an industrial waste material that has been studied by many researchers for use as fine concrete aggregate. As one example of its potential application, nuclear power plants and radioactive waste disposal sites are often located in areas vulnerable to attack by chloride and sulfate, and this may compromise the durability of the concrete structure designed to shield radiation. More durable concrete would therefore be desirable. We studied the durability of concrete mixed with waste glass through the following approach. Waste CRT glass containing heavy metals was recycled as fine aggregate for concrete; the durability of the concrete was investigated by performing freeze-thaw resistance, sulfate attack, and chloride ion penetration measurement. The test results showed that as the mixing ratio of waste glass increased, the freezing and thawing resistance, sulfate attack resistance, and chloride ion penetration resistance were all better in the concrete containing waste glass than in normal concrete. However, the compressive and the flexural strength of the concrete both decreased due to lower adhesion between cement paste and waste glass. In conclusion, it was confirmed that concrete substituted with heavyweight waste glass could be used in radiation shielding structures.

Hypoxic-ischemic (HI) brain injury and spinal cord injury (SCI) lead to extensive tissue loss and axonal degeneration. The combined application of the polymer scaffold and neural progenitor cells (NPCs) has been reported to enhance neural repair, protection and regeneration through multiple modes of action following neural injury. This study investigated the reparative ability and therapeutic potentials of biological bridges composed of human fetal brain-derived NPCs seeded upon poly(glycolic acid)-based scaffold implanted into the infarction cavity of a neonatal HI brain injury or the hemisection cavity in an adult SCI. Implantation of human NPC (hNPC)–scaffold complex reduced the lesion volume, induced survival, engraftment, and differentiation of grafted cells, increased neovascularization, inhibited glial scar formation, altered the microglial/macrophage response, promoted neurite outgrowth and axonal extension within the lesion site, and facilitated the connection of damaged neural circuits. Tract tracing demonstrated that hNPC–scaffold grafts appear to reform the connections between neurons and their targets in both cerebral hemispheres in HI brain injury and protect some injured corticospinal fibers in SCI. Finally, the hNPC–scaffold complex grafts significantly improved motosensory function and attenuated neuropathic pain over that of the controls. These findings suggest that, with further investigation, this optimized multidisciplinary approach of combining hNPCs with biomaterial scaffolds provides a more versatile treatment for brain injury and SCI., Tissue engineering: Repairing brain and spinal injuries Biodegradable scaffolds seeded with human fetal brain cells can help repair neurological injuries in rodents. A team led by Kook In Park and Il-Shin Lee from the Yonsei University College of Medicine in Seoul, South Korea, created a mesh of plastic fibers that they bathed in neural progenitor cells. Over the course of several days, these cells differentiated into different types of brain cells, including neurons and glia. The researchers implanted these cell-scaffold complexes into the sites of injury in two rodent models: newborn mice with oxygen deprivation to the brain, and adult rats with severed spinal cords. In both cases, the treatment helped the injured tissues heal and improved the neurological or motor function of the animals. The authors suggest these tissue-engineered structures could also help people with brain or spine injuries.

Cell-based therapies are attractive for treating various degenerative disorders and cancer but delivering functional cells to the region of interest in vivo remains difficult. The problem is exacerbated in dense biological matrices such as solid tissues because these environments impose significant steric hindrances for cell movement. Here, we show that neural stem cells transfected with zinc-doped ferrite magnetic nanoparticles (ZnMNPs) can be pulled by an external magnet to migrate to the desired location in the brain. These magnetically labeled cells (Mag-Cells) can migrate because ZnMNPs generate sufficiently strong mechanical forces to overcome steric hindrances in the brain tissues. Once at the site of lesion, Mag-Cells show enhanced neuronal differentiation and greater secretion of neurotrophic factors than unlabeled control stem cells. Our study shows that ZnMNPs activate zinc-mediated Wnt signaling to facilitate neuronal differentiation. When implemented in a rodent brain stroke model, Mag-Cells led to significant recovery of locomotor performance in the impaired limbs of the animals. Our findings provide a simple magnetic method for controlling migration of stem cells with high therapeutic functions, offering a valuable tool for other cell-based therapies.

In this study, the reinforced concrete rahmen bridge damaged by the chloride attack was investigated. According to the investigation, the degraded concretes on cantilever kerb and end part were intensively observed. Thus, the chloride content test and half-cell method were performed to evaluate the degraded parts. As a result, the contents of chloride on degraded parts were C and D grade. On the other hand, the half-cell potential values of rebar in degraded concrete were measured with the minor corrosion. This rebar corrosion is expected to progressing. Chloride content D grade is due to expansion pressure by corrosion of rebar and freeze-thaw by permeate water, could see progresses rapidly degradation. In order to prevent chloride attack to concrete deck caused by deicing salts, corresponding to the chloride critical concentration must maintain grade b or at least grade c. Chloride condition evaluation standard apply to evaluation of marine structure chloride attack with chloride attack by deicing salts.

Background Alzheimer’s disease (AD) is an inexorable neurodegenerative disease that commonly occurs in the elderly. The cognitive impairment caused by AD is associated with abnormal accumulation of amyloid-β (Aβ) and hyperphosphorylated tau, which are accompanied by inflammation. Neural stem cells (NSCs) are self-renewing, multipotential cells that differentiate into distinct neural cells. When transplanted into a diseased brain, NSCs repair and replace injured tissues after migration toward and engraftment within lesions. We investigated the therapeutic effects in an AD mouse model of human NSCs (hNSCs) that derived from an aborted human fetal telencephalon at 13 weeks of gestation. Cells were transplanted into the cerebral lateral ventricles of neuron-specific enolase promoter-controlled APPsw-expressing (NSE/APPsw) transgenic mice at 13 months of age. Results Implanted cells extensively migrated and engrafted, and some differentiated into neuronal and glial cells, although most hNSCs remained immature. The hNSC transplantation improved spatial memory in these mice, which also showed decreased tau phosphorylation and Aβ42 levels and attenuated microgliosis and astrogliosis. The hNSC transplantation reduced tau phosphorylation via Trk-dependent Akt/GSK3β signaling, down-regulated Aβ production through an Akt/GSK3β signaling-mediated decrease in BACE1, and decreased expression of inflammatory mediators through deactivation of microglia that was mediated by cell-to-cell contact, secretion of anti-inflammatory factors generated from hNSCs, or both. The hNSC transplantation also facilitated synaptic plasticity and anti-apoptotic function via trophic supplies. Furthermore, the safety and feasibility of hNSC transplantation are supported. Conclusions These findings demonstrate the hNSC transplantation modulates diverse AD pathologies and rescue impaired memory via multiple mechanisms in an AD model. Thus, our data provide tangible preclinical evidence that human NSC transplantation could be a safe and versatile approach for treating AD patients. Electronic supplementary material The online version of this article (doi:10.1186/s13024-015-0035-6) contains supplementary material, which is available to authorized users.

In a phase I/IIa open-label and nonrandomized controlled clinical trial, we sought to assess the safety and neurological effects of human neural stem/progenitor cells (hNSPCs) transplanted into the injured cord after traumatic cervical spinal cord injury (SCI). Of 19 treated subjects, 17 were sensorimotor complete and 2 were motor complete and sensory incomplete. hNSPCs derived from the fetal telencephalon were grown as neurospheres and transplanted into the cord. In the control group, who did not receive cell implantation but were otherwise closely matched with the transplantation group, 15 patients with traumatic cervical SCI were included. At 1 year after cell transplantation, there was no evidence of cord damage, syrinx or tumor formation, neurological deterioration, and exacerbating neuropathic pain or spasticity. The American Spinal Injury Association Impairment Scale (AIS) grade improved in 5 of 19 transplanted patients, 2 (A → C), 1 (A → B), and 2 (B → D), whereas only one patient in the control group showed improvement (A → B). Improvements included increased motor scores, recovery of motor levels, and responses to electrophysiological studies in the transplantation group. Therefore, the transplantation of hNSPCs into cervical SCI is safe and well-tolerated and is of modest neurological benefit up to 1 year after transplants. This trial is registered with Clinical Research Information Service (CRIS), Registration Number:KCT0000879.

Devising efficient gene delivery systems is crucial to enhancing the therapeutic efficacy of gene–cell therapy approaches. Herein, inverted quasi-spherical (iQS) droplet systems, which enhance gene delivery efficiencies by reducing the path lengths of gene vectors, mediating motions of vectors at early stages, and raising the contact frequencies of vectors with cells, are developed by adopting the principle of 3D hanging-drop cell culture. Micrometer-sized polydopamine (pDA) holes are created on superhydrophobic titanium isopropoxide (TiO2)-coated substrates by physical scraping; droplets are loaded on the pDA holes, and inversion of the substrate generates iQS droplets with large contact angles. Both human neural stem cells (hNSCs) and adeno-associated viral vectors are simultaneously incorporated into the iQS droplets to assess gene delivery efficiencies. The steep angles of iQS droplets and enhanced cell/vector contact frequencies facilitate the viral association with hNSCs and enhancing cell–cell interactions, thereby significantly promoting gene delivery efficiencies. Even with reduced viral quantities/exposure times and cell numbers, the iQS droplet systems elicit sufficient gene expression (i.e., interleukin-10). The ability of the iQS droplet systems to maximize beneficial gene delivery effects with minimal materials (e.g., medium, cells, and vectors) should enable their extensive use as a platform for preparing genetically stimulated cellular therapeutics.

Neural stem cells (NSCs) are characterized by a capacity for self-renewal, differentiation into multiple neural lineages, all of which are considered to be promising components for neural regeneration. However, for cell-replacement therapies, it is essential to monitor the process of in vitro NSC differentiation and identify differentiated cell phenotypes. We report a real-time and label-free method that uses a capacitance sensor array to monitor the differentiation of human fetal brain-derived NSCs (hNSCs) and to identify the fates of differentiated cells. When hNSCs were placed under proliferation or differentiation conditions in five media, proliferating and differentiating hNSCs exhibited different frequency and time dependences of capacitance, indicating that the proliferation and differentiation status of hNSCs may be discriminated in real-time using our capacitance sensor. In addition, comparison between real-time capacitance and time-lapse optical images revealed that neuronal and astroglial differentiation of hNSCs may be identified in real-time without cell labeling.

Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal brain-derived NSPCs possess some therapeutic effect for TLE treatments although further studies to both increase the yield of NSPC grafts-derived functionally integrated GABAergic neurons and improve cognitive deficits are still needed.

Patient Female, 51 FINAL DIAGNOSIS: Patological skin picking Symptoms: Aphasia • headache • hemiparesis • incontinence Medication - Clinical Procedure: - Specialty: Dermatology. Objective Challenging differential diagnosis. Background Pathological skin picking (PSP) disorder is characterized by repetitive and compulsive picking of the skin resulting in tissue damage. PSP has been shown to affect 5.4% of a community sample, 4% of college students, and 2% of patients seen in a dermatology clinic. It can be associated with significant disfigurement. The diagnosis requires obtaining a careful history and high clinical suspicion. Case report We report a previously healthy 51-year-old Caucasian female with a history of "acne" who presented with new onset right-sided hemiparesis, mild aphasia and an episode of incontinence. She had memory loss of the prior few days. She also complained of a four-day history of intense headaches and dizziness. CT and MRI of the head showed encephalomalacia involving the left frontal and parietal lobes. Further history from the patient revealed that the patient had been picking at her forehead with a sewing needle and later with a long knitting needle. Conclusions PSP is a prevalent disorder, which can have potentially serious health consequences. Besides potential disfigurement and scarring, PSP can have significant morbidity and mortality. Early diagnosis and appropriate treatment by clinicians are essential to prevent potentially fatal consequences.

Neural stem cells (NSCs) are characterized by a capacity for self-renewal, differentia tion into multiple neural cell lineages, and migration toward damaged sites in the central nervous system (CNS). NSCs expanded in culture could be implanted into the brain where they integrate into host neural circuitry and stably express foreign genes. It hence appears that transplantation of NSCs has been proposed as a promising therapeutic strategy in neurological disorders. During hypoxic-ischemic (HI) brain injury, factors are transiently elaborated to which NSCs respond by migrating to degenerating regions and differentiating towards replacement of dying neural cells. In addition, NSCs serve as vehicles for gene delivery and appear capable of simultaneous neural cell replacement and gene therapy (e.g. with factors that might enhance neuronal differentiation, neurites outgrowth, proper connectivity, neuroprotection, and/or immunomodulatory substances). When combined with certain synthetic biomaterials, NSCs may be even more effective in ‘engineering’ the damaged CNS towards reconstitution. Human NSCs were isolated from the forebrain of an aborted fetus at 13 weeks of gestation and were grown as neuro spheres in cultures. After the characterization of human NSCs in preclinical testing and the approval of the IRB, a clinical trial of the transplantation of human NSCs into patients with severe perinatal HI brain injury has been performed. The existing data from these clinical trials have shown to be safe, well tolerated, and of neurologicallysome benefits. Therefore, long-term and large scale multicenter clinical study is required to determine its precise therapeutic effect and safety.

Neural progenitor cells (NPs) have shown several promising benefits for the treatment of neurological disorders. To evaluate the therapeutic potential of human neural progenitor cells (hNPs) in amyotrophic lateral sclerosis (ALS), we transplanted hNPs or growth factor (GF)-expressing hNPs into the central nervous system (CNS) of mutant Cu/Zn superoxide dismutase (SOD1(G93A)) transgenic mice. The hNPs were engineered to express brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), VEGF, neurotrophin-3 (NT-3), or glial cell-derived neurotrophic factor (GDNF), respectively, by adenoviral vector and GDNF by lentiviral vector before transplantation. Donor-derived cells engrafted and migrated into the spinal cord or brain of ALS mice and differentiated into neurons, oligodendrocytes, or glutamate transporter-1 (GLT1)-expressing astrocytes while some cells retained immature markers. Transplantation of GDNF- or IGF-1-expressing hNPs attenuated the loss of motor neurons and induced trophic changes in motor neurons of the spinal cord. However, improvement in motor performance and extension of lifespan were not observed in all hNP transplantation groups compared to vehicle-injected controls. Moreover, the lifespan of GDNF-expressing hNP recipient mice by lentiviral vector was shortened compared to controls, which was largely due to the decreased survival times of female animals. These results imply that although implanted hNPs differentiate into GLT1-expressing astrocytes and secrete GFs, which maintain dying motor neurons, inadequate trophic support could be harmful and there is sexual dimorphism in response to GDNF delivery in ALS mice. Therefore, additional therapeutic approaches may be required for full functional recovery.

Neural stem cells (NSCs) are operationally defined by their ability to self-renew, to differentiate into cells of all glial and neuronal lineages throughout the neuraxis, and to populate developing or degenerating central nervous system (CNS) regions. Thus their use as graft material can be considered analogous to hematopoietic stem cell-mediated reconstitution and gene transfer. The recognition that NSCs propagated in culture could be reimplanted into mammalian brain, where they might integrate appropriately throughout the mammalian CNS and stably express foreign genes, has unveiled a new role for neural transplantation and gene therapy and a possible strategy for addressing the CNS manifestations of diseases that heretofore had been refractory to intervention. NSCs additionally have the appealing ability to home in on pathology, even over great distances. Such observations help to advance the idea that NSCs--as a prototype for stem cells from other solid organs--might aid in reconstructing the molecular and cellular milieu of maldeveloped or damaged CNS.