Quantitative Multimodal Evaluation of Passaging Human Neural Crest Stem Cells for Peripheral Nerve Regeneration

Peripheral nerve injury is a major burden to societies worldwide, however, current therapy options (e.g. autologous nerve grafts) are unable to produce satisfactory outcomes. Many studies have shown that stem cell transplantation holds great potential for peripheral nerve repair, and human neural crest stem cells (hNCSCs), which give rise to a variety of tissues in the peripheral nervous system, are particularly promising. NCSCs are one of the best candidates for clinical translation, however, to ensure the viability and quality of NCSCs for research and clinical use, the effect of in vitro cell passaging on therapeutic effects needs be evaluated given that passaging is required to expand NCSCs to meet the demands of transplantation in preclinical research and clinical trials. To date, no study has investigated the quality of NCSCs past the 5th passage in vivo. In this study, we employed a multimodal evaluation system to investigate changes in outcomes between transplantation with 5th (p5) and 6th passage (p6) NCSCs in a 15 mm rat sciatic nerve injury and repair model. Using CatWalk gait analysis, gastrocnemius muscle index, electrophysiology, immunohistochemistry, and histomorphometric analysis, we showed that p6 NCSCs demonstrated decreased cell survival, Schwann-cell differentiation, axonal growth, and functional outcomes compared to p5 NCSCs (all p?<?0.05). In conclusion, p6 NCSCs showed significantly reduced therapeutic efficacy compared to p5 NCSCs for peripheral nerve regeneration.     

Rapid Pore Cranial Drilling With External Ventricular Drainage for Treatment of Intraventricular Hemorrhage: A 36-Year Case Series

This study aimed to describe the technique details of rapid pore cranial drilling with external ventricular drainage and document its clinical outcomes by highlighting the advantages over the traditional and modified cranial drilling technique. Intraventricular hemorrhage is one of the most severe subtypes of hemorrhagic stroke with high mortality. The amount of blood in the ventricles is associated with severity of outcomes, and fast removal of the blood clot is the key to a good prognosis. Between 1977 and 2013, 3773 patients admitted for intraventricular hemorrhage underwent rapid pore cranial drilling drainage. The therapeutic effects and clinical outcomes were retrospectively analyzed. Of these patients, 1049 (27.8%) experienced complete remission, 1788 (47.4%) had improved condition, and 936 (24.8%) died. A total of 3229 (85.6%) patients gained immediate remission. One typical case was illustrated to demonstrate the efficacy of the rapid pore drilling technique. Rapid pore cranial drilling drainage in patients with intraventricular hemorrhage is fast, effective, and provides immediate relief in patients with severe conditions. It could be a better alternative to the conventional drilling approach for treatment of intraventricular hemorrhage. A randomized controlled trial for direct comparison between the rapid pore cranial drilling drainage and conventional drilling technique is in urgent need.Key words: Intraventricular hemorrhage, External ventricular drainage, Rapid pore cranial drillingIntraventricular hemorrhage (IVH) denotes a bleeding within the ventricular system of the brain. It usually results from traumatic brain injuries or hemorrhagic stroke, and the prognosis can be very poor.^1,2 Volume of IVH has been reported to be a predictor of outcome in patients with spontaneous intracerebral hemorrhage (ICH) and extension to the ventricles.^3,4 Epidemiologic data has demonstrated a strong association between the amount of blood in the ventricles and severity of outcomes including mortality, coma, and functional impairment.⁴ This finding provides substantial support for the therapeutic idea of intraventricular hematoma removal, which has been validated in animal studies. The removal of blood clot from ventricles prevents hydrocephalus and inhibits inflammation mediated progressive tissue damage.^5,6 External ventricular drainage (EVD), also known as ventriculostomy, has then been developed to remove the blood or obstructed cerebrospinal fluid (CSF) from the ventricles of the brain, which thus relieves the elevated intracranial pressure (ICP) and hydrocephalus.⁷ Efforts have been made to improve the drilling and drainage techniques. For example, the method of percutaneous needle trephination has been introduced and performed in case of emergency as a simple, low-risk, effective way to reduce ICP.^8,9 Similarly, Zhang et al first introduced a medical device named rapid pore drilling apparatus in 1975, and shortly after reported the first success using the rapid pore drilling technique to perform EVD via the frontal horn of the lateral ventricle, which saved the life of a patient with IVH and severe tonsillar hernia.^10,11 It was a fast procedure, completed within 10 minutes, and could be performed at the bedside under sterile condition. Since then, this technique has been adopted in many hospitals in Shandong Province, China. In this study, we collected and analyzed clinical data on 3773 patients who were admitted for IVH at 14 hospitals from 1977 to 2013 and received rapid pore cranial drilling with EVD. The clinical experiences, including operating procedures, duration, technical performances, and the therapeutic effect of rapid pore drilling with EVD were recorded. To our best knowledge, the present study was the biggest one that involved the largest cohort so far and summarized the clinical practice of the rapid pore cranial drilling technique over 30 years. The results indicate that the rapid pore cranial drilling technique is minimally invasive, fast, safe, and effective for treating patients with severe IVH.     

双氢青蒿素对人骨肉瘤细胞TE85细胞内尿激酶型纤溶酶原激活物和色素上皮衍生因子表达的影响

目的 观察双氢青蒿素(DHA)对人骨肉瘤细胞活性、转移能力以及细胞中尿激酶型纤溶酶原激活物(uPA)和色素上皮衍生因子(PEDF)表达的影响.方法 将不同浓度的DHA(5、10、20、40、80 μmol/L)作用于体外培养的正常人成骨细胞和人骨肉瘤细胞TE85 12、24、48 h后,噻唑蓝(MTT)法测定DHA对细胞活性的影响,反转录-聚合酶链反应(RT-PCR)法检测细胞中uPA和PEDF mRNA水平的表达,Westen blot法检测uPA和PEDF蛋白水平的表达.结果 DHA对人成骨细胞活性无明显影响(P＞0.05).DHA能够明显抑制人骨肉瘤细胞TE85的活性(P＜0.05).不同作用时间下DHA对人骨肉瘤细胞TE85的半数抑制浓度(IC50)分别为(12 h)=(41.66±0.53) μmol/L、IC50(24 h)=(32.28 ±0.27)μmol/L和IC50 (48 h)=(22.53±1.26) μmol/L.DHA能够明显减少人骨肉瘤细胞的迁移和细胞中uPA的表达水平,同时细胞中PEDF表达升高(P＜0.05).结论 DHA对正常人体骨组织无害,能够有效抑制骨肉瘤细胞生长和转移.     

Expansion of the mutation and phenotypic spectrum of hereditary spastic paraplegia

Neurological Sciences - Hereditary spastic paraplegias (HSPs) are a heterogeneous group of rare neurodegenerative disorders affecting the corticospinal tracts, and more than 80 HSP loci have been...