We tested the feasibility and safety of human-spinal-cord-derived neural stem cell (NSI-566) transplantation for the treatment of chronic spinal cord injury (SCI). In this clinical trial, four subjects with T2-T12 SCI received treatment consisting of removal of spinal instrumentation, laminectomy, and durotomy, followed by six midline bilateral stereotactic injections of NSI-566 cells. All subjects tolerated the procedure well and there have been no serious adverse events to date (18-27 months post-grafting). In two subjects, one to two levels of neurological improvement were detected using ISNCSCI motor and sensory scores. Our results support the safety of NSI-566 transplantation into the SCI site and early signs of potential efficacy in three of the subjects warrant further exploration of NSI-566 cells in dose escalation studies. Despite these encouraging secondary data, we emphasize that this safety trial lacks statistical power or a control group needed to evaluate functional changes resulting from cell grafting.

Background: Operative management of lower back pain often necessitates anterior lumbar interbody fusion (ALIF) or transforaminal lumbar interbody fusion (TLIF). Specific pathoanatomic advantages and indications exist for both approaches, and few studies to date have characterized comparative early outcomes. Methods: Adult patients undergoing elective ALIF or TLIF operations were abstracted from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) years 2011-2014. Univariate analyses were performed by surgery cohort for each outcome and adjusted for demographic/clinical variables (age ! 65, sex, race, body mass index, American Society of Anesthesiologists physical classification score, functional status, inpatient/outpatient status, smoking, hypertension, Charlson Comorbidity Index) using multivariable regression. Means, standard errors, mean differences (B), odds ratios (ORs), and associated 95% confidence intervals (CIs) are reported. Significance was assessed at P , .05. Results: Of 8263 subjects (ALIF: 4325, TLIF: 3938), ALIF subjects were younger, less obese, less physically impaired, and had significantly lower rates of hypertension, diabetes, coagulopathy, and previous cardiac surgery. On multivariable analysis, ALIF associated with shorter operative time (B ¼À11.80 minutes, 95% CI [À16.48, À7.12]; P , .001). Transforaminal lumbar interbody fusion was associated with increased incidence of urinary tract infections (UTIs; OR ¼ 1.57, 95% CI [1.10, 2.26]; P ¼ .013) and of blood transfusions (OR ¼ 1.19, 95% CI [1.04, 1.37]; P ¼ .012). Multivariate analysis also demonstrated TLIF associated with shorter hospital length of stay (B ¼À0.27 days, 95% CI [À0.54, À0.01]; P ¼ .041), and fewer cases of pneumonia (OR ¼ 0.55, 95% CI [0.32, 0.94]; P ¼ .029) and prolonged ventilator dependency (OR ¼ 0.33, 95% CI [0.12, 0.84]; P ¼ .021). Conclusions: Comparatively, ALIF patients experienced decreased operative time and decreased incidence of postoperative UTIs and blood transfusions. Anterior lumbar interbody fusion patients were more likely to suffer postoperative pulmonary complications and longer hospital stays. Our data support the notion that both anterior and transforaminal surgical approaches perform comparably in context of 30-day perioperative outcomes.

Effective in vivo use of adeno-associated virus (AAV)-based vectors to achieve gene-specific silencing or upregulation in the central nervous system has been limited by the inability to provide more than limited deep parenchymal expression in adult animals using delivery routes with the most clinical relevance (intravenous or intrathecal). Here, we demonstrate that the spinal pia membrane represents the primary barrier limiting effective AAV9 penetration into the spinal parenchyma after intrathecal AAV9 delivery. We develop a novel subpial AAV9 delivery technique and AAV9-dextran formulation. We use these in adult rats and pigs to show (i) potent spinal parenchymal transgene expression in white and gray matter including neurons, glial and endothelial cells after single bolus subpial AAV9 delivery; (ii) delivery to almost all apparent descending motor axons throughout the length of the spinal cord after cervical or thoracic subpial AAV9 injection; (iii) potent retrograde transgene expression in brain motor centers (motor cortex and brain stem); and (iv) the relative safety of this approach by defining normal neurological function for up to 6 months after AAV9 delivery. Thus, subpial delivery of AAV9 enables gene-based therapies with a wide range of potential experimental and clinical utilizations in adult animals and human patients.