Adult human adipose-derived mesenchymal stem cells (hAMSCs) are multipotent cells, which are abundant, easily collected, and bypass the ethical concerns that plague embryonic stem cells. Their utility and accessibility have led to the rapid development of clinical investigations to explore their autologous and allogeneic cellular-based regenerative potential, tissue preservation capabilities, anti-inflammatory properties, and anticancer properties, among others. hAMSCs are typically cultured under ambient conditions with 21% oxygen. However, physiologically, hAMSCs exist in an environment of much lower oxygen tension. Furthermore, hAMSCs cultured in standard conditions have shown limited proliferative and migratory capabilities, as well as limited viability. This study investigated the effects hypoxic culture conditions have on primary intraoperatively derived hAMSCs. hAMSCs cultured under hypoxia (hAMSCs-H) remained multipotent, capable of differentiation into osteogenic, chondrogenic, and adipogenic lineages. In addition, hAMSCs-H grew faster and exhibited less cell death. Furthermore, hAMSCs-H had greater motility than normoxia-cultured hAMSCs and exhibited greater homing ability to glioblastoma (GBM) derived from brain tumor-initiating cells from our patients in vitro and in vivo. Importantly, hAMSCs-H did not transform into tumor-associated fibroblasts in vitro and were not tumorigenic in vivo. Rather, hAMSCs-H promoted the differentiation of brain cancer cells in vitro and in vivo. These findings suggest an alternative culturing technique that can enhance the function of hAMSCs, which may be necessary for their use in the treatment of various pathologies including stroke, myocardial infarction, amyotrophic lateral sclerosis, and GBM.

The reported incidence of meniscal tears is approximately 61 per 100,000. In instances where preservation of the native meniscus is no longer a feasible option, meniscal allograft transplantation (MAT) and implants or scaffolds may be considered. The goal of this review was to compare the success and failure rates of two techniques, MAT and meniscal scaffolds, and make an inference which treatment is more preferable at the present time and future. Studies that met inclusion criteria were assessed for technique used, type of transplant used, number of procedures included in the study, mean age of patients, mean follow-up time, number of failures, failure rate, and reported reoperation rate. Fifteen studies for the MAT group and 7 studies for the meniscal scaffold group were identified. In this selection of studies, the average failure rate in the MAT group was 18.7% and average reoperation rate was 31.3%. The average failure rate in the meniscal scaffold group was 5.6%, and average reoperation rate was 6.9%. It appears that although MAT is associated with high reoperation and failure rates, the limited number of studies on both MAT and scaffolds and mainly short-term results of scaffold studies make it difficult to make an objective comparison.

Object Historically, adult degenerative lumbar scoliosis (DLS) has been treated with multilevel decompression and instrumented fusion to reduce neural compression and stabilize the spinal column. However, due to the profound morbidity associated with complex multilevel surgery, particularly in elderly patients and those with multiple medical comorbidities, minimally invasive surgical approaches have been proposed. The goal of this meta-analysis was to review the differences in patient selection for minimally invasive surgical versus open surgical procedures for adult DLS, and to compare the postoperative outcomes following minimally invasive surgery (MIS) and open surgery. Methods In this meta-analysis the authors analyzed the complication rates and the clinical outcomes for patients with adult DLS undergoing complex decompressive procedures with fusion versus minimally invasive surgical approaches. Minimally invasive surgical approaches included decompressive laminectomy, microscopic decompression, lateral and extreme lateral interbody fusion (XLIF), and percutaneous pedicle screw placement for fusion. Mean patient age, complication rates, reoperation rates, Cobb angle, and measures of sagittal balance were investigated and compared between groups. Results Twelve studies were identified for comparison in the MIS group, with 8 studies describing the lateral interbody fusion or XLIF and 4 studies describing decompression without fusion. In the decompression MIS group, the mean preoperative Cobb angle was 16.7° and mean postoperative Cobb angle was 18°. In the XLIF group, mean pre- and postoperative Cobb angles were 22.3° and 9.2°, respectively. The difference in postoperative Cobb angle was statistically significant between groups on 1-way ANOVA (p = 0.014). Mean preoperative Cobb angle, mean patient age, and complication rate did not differ between the XLIF and decompression groups. Thirty-five studies were identified for inclusion in the open surgery group, with 18 studies describing patients with open fusion without osteotomy and 17 papers detailing outcomes after open fusion with osteotomy. Mean preoperative curve in the open fusion without osteotomy and with osteotomy groups was 41.3° and 32°, respectively. Mean reoperation rate was significantly higher in the osteotomy group (p = 0.008). On 1-way ANOVA comparing all groups, there was a statistically significant difference in mean age (p = 0.004) and mean preoperative curve (p = 0.002). There was no statistically significant difference in complication rates between groups (p = 0.28). Conclusions The results of this study suggest that surgeons are offering patients open surgery or MIS depending on their age and the severity of their deformity. Greater sagittal and coronal correction was noted in the XLIF versus decompression only MIS groups. Larger Cobb angles, greater sagittal imbalance, and higher reoperation rates were found in studies reporting the use of open fusion with osteotomy. Although complication rates did not significantly differ between groups, these data are difficult to interpret given the heterogeneity in reporting complications between studies.

Clinically relevant concentrations and incubation times of isoflurane could promote the viability and mobility of U251-GSCs, suggesting this general anaesthetic may have detrimental effects in glioblastoma by facilitating its growth and migration.

Patients with cerebellar metastases have more distinct clinical presentations and outcomes than patients with non-cerebellar lesions. The findings of this study may help risk stratify and guide treatment regimens aimed at maximizing outcomes for patients with cerebellar metastases.

Mesenchymal stem cells (MSCs) and neural progenitor cells (NPCs) have been regarded for their clinical therapeutic potential for central nervous system (CNS) pathologies. Their potential utility is a result of their intrinsic ability to repair damaged tissues, deliver therapeutic proteins, and migrate to sites of pathology within the brain. However, it remains unclear whether the CNS promotes any changes in these potential therapeutic cells, which would be critical to understand before clinical application. A major component of the CNS is cerebrospinal fluid (CSF). Therefore, the aim of this study was to evaluate the influence that human CSF has on the function of human adipose-derived MSCs (hAMSCs) and human fetal-derived NPCs (hfNPCs) in regard to cell proliferation, survival, and migration. This study demonstrated that human noncancerous CSF promoted proliferation and inhibited apoptosis of hAMSCs and hfNPCs. Preculturing these stem cells in human CSF also increased their migratory speed and distance traveled. Furthermore, insulin-like growth factor-1 (IGF-1) in human CSF enhanced the migration capacity and increased the expression of C-X-C chemokine receptor type 4 (CXCR4) in both stem cell types. These current findings highlight a simple and natural way in which human CSF can enhance the proliferation, migration, and viability of human exogenous primary hAMSCs and hfNPCs. This study may provide insight into improving the clinical efficacy of stem cells for the treatment of CNS pathologies.

Glioblastoma (GBM) remains the most common and lethal intracranial tumor. In a comparison of gene expression by A2B5-defined tumor-initiating progenitor cells (TPCs) to glial progenitor cells derived from normal adult human brain, we found that the F2R gene encoding PAR1 was differentially overexpressed by A2B5-sorted TPCs isolated from gliomas at all stages of malignant development. In this study, we asked if PAR1 is causally associated with glioma progression. Lentiviral knockdown of PAR1 inhibited the expansion and self-renewal of human GBM-derived A2B5+ TPCs in vitro, while pharmacological inhibition of PAR 1 similarly slowed both the growth and migration of A2B5+ TPCs in culture. In addition, PAR1 silencing potently suppressed tumor expansion in vivo, and significantly prolonged the survival of mice following intracranial transplantation of human TPCs. These data strongly suggest the importance of PAR1 to the self-renewal and tumorigenicity of A2B5-defined glioma TPCs; as such, the abrogation of PAR1-dependent signaling pathways may prove a promising strategy for gliomas.

Neurosurg Focus 40 (4):E14, 2016M any sports-related brain injuries involve mild traumatic brain injuries (mTBIs), which result from physical blows to the head sustained over a period of time. Sports associated with an increased risk of head injury include American football, ice hockey, soccer, rugby, the martial arts, boxing, and bicycling. 21,90 These injuries are often unrecognized, undiagnosed, or underreported, which reflects the fact that this is a growing medical concern, often labeled a "silent epidemic." 8,66 Chronic exposure to mild brain injuries can result in long-term neurological consequences and represents a spectrum of disorders. The most remarkable outcome of mTBI is termed chronic traumatic encephalopathy (CTE), a clinical syndrome that is associated with neurodegeneration and behavioral, cognitive, and/or motor deficits. Although this disease has distinct pathological features, CTE is considered a diagnosis of exclusion because only postmortem biopsies can confirm the diagnosis. Therefore, new diagnostic methods need to be developed to: 1) inform patients of a definitive diagnosis, 2) better understand the epidemiology and risk factors of the disease, and 3) implement intervention programs to prevent any potential long-term complications. This review examines how understanding the pathology and molecular changes associated with repeated head trauma can lead to the discovery of novel imaging techniques and biomarkers. Mild Traumatic Brain Injury and CTEChronic traumatic encephalopathy has evolved from the so-called punch-drunk syndrome, which was used to describe a distinct neuropsychiatric condition that seemed to affect boxers, eventually becoming known as dementia pugilistica during the 1920s and 1930s. Symptoms such ABBrEvIATIoNs AD = Alzheimer's disease; APOE = apolipoprotein E; ASL = arterial spin labeling; BBB = blood-brain barrier; BOLD = blood oxygen level-dependent; CA = cornu ammonis; CTE = chronic traumatic encephalopathy; DTI = diffusion tensor imaging; FA = fractional anisotropy; fMRI = functional MRI; GFAP = glial fibrillary acidic protein; GRE = gradient recall echo; miRNA = microRNA; MRS = MR spectroscopy; mTBI = mild traumatic brain injury; NFL = National Football League; NFT = neurofibrillary tangle; NINDS = National Institute of Neurological Disorders and Stroke; NSE = neuron-specific enolase; p-tau = phosphorylated tau; SWI = susceptibility-weighted imaging; TDP-43 = TAR DNA-binding protein 43;18 F-FDDNP = 2-(1-{6- [(2-[fluorine-18] Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profo...