Significance: We developed a platform technology to determine therapeutic mechanisms of human mesenchymal stromal stem cells (hMSCs) in a dorsal root ganglion coculture system and an intraspinal cord implantation model. The unique poly(lactic- co- glycolic) acid scaffolding augments hMSC stemness, engraftment, and function without neural transdifferentiation or mesenchymal lineage development, resulting in robust motosensory improvement, pain and tissue damage mitigation, and myelin preservation in adult rat spinal cord after injury. The scaffolded hMSC-derived neurotrophism, neurogenesis, angiogenesis, antiautoimmunity, and antiinflammation support the propriospinal network, neuromuscular junctions, and serotonergic reticulospinal reinnervation to activate the central pattern generator for restoring hindlimb locomotion. Our findings illuminate “recovery neurobiology”—i.e., the injured spinal cord may deploy polysynaptic neural circuits different from normal adulthood pathways for postinjury improvement.

Intervertebral disk (IVD) degeneration is a common, chronic, and complex degeneration process that frequently leads to back pain and disability, resulting in a major public health issue. In this review we describe biological therapies under preclinical or clinical development with an emphasis on stem cell-based multimodal approaches that target prevention and treatment of IVD degeneration. Systematical review of the basic science and clinical literature was performed to summarize the current status of devising biological approaches to treating IVD degeneration. Since the exact mechanisms underlying IVD degeneration have not yet been fully elucidated and conservative managements appear to be mostly ineffective, current surgical treatment focuses on removal of the pathological disk tissues combined with spinal fusion. The treatment options, however, often produce insufficient efficacy and even serious complications. Therefore, there have been growing demands and endeavors for developing novel regenerative biology-guided strategies for repairing the IVD via delivery of exogenous growth factors, introduction of therapeutic genes, and transplantation of stem cells, or combinatorial therapies. Overall, the data suggest that when applied under a recovery neurobiology principle, multimodal regimens comprising ex vivo engineered stem cell-based disks hold a high potential promise for efficacious clinical translations.

OBJECTIVE: The opioid crisis is identified as a national emergency and epidemic in the United States. The aim of this study was to identify risk factors associated with opioid dependence in patients undergoing surgery for degenerative spondylolisthesis (DS).METHODS: The authors queried MarketScan databases to investigate the factors affecting postsurgery opioid use in patients with DS between 2000 and 2012. The outcome of interest was opioid dependence, which was defined as continued opioid use, > 10 opioid prescriptions, or diagnosis of or prescription for opioid dependence disorder in the period of 1 year before or 3–15 months after the procedure. Comparisons of outcomes were performed using nonparametric 2-group tests and generalized regression models.RESULTS: A cohort of 10,708 patients was identified from the database. The median patient age was 61 years (interquartile range 54–69 years), and 65.1% were female (n = 6975). A majority of patients had decompression with fusion (n = 10,068; 94%) and underwent multilevel procedures (n = 8123; 75.9%). Of 10,708 patients, 14.85% (n = 1591) were identified as having opioid dependence within 12 months prior to the index surgical procedure and 9.90% (n = 1060) were identified as having opioid dependence within 3–15 months after the procedure. Of all the variables, prior opioid dependence (OR 16.29, 95% CI 14.10–18.81, p < 0.001) and younger age (1-year increase in age: OR 0.972, 95% CI 0.963–0.980, p < 0.001) were independent predictors of opioid dependence following surgery for DS. The use of fusion was not associated with opioid dependence following the procedure (p = 0.8396). Following surgery for DS, patients were more likely to become opioid independent than they were to become opioid dependent (8.54% vs 3.58%, p < 0.001).CONCLUSIONS: The majority of patients underwent fusion for DS. Surgical decompression with fusion was not associated with increased risk of postsurgery opioid dependence in patients with DS. Overall, opioid dependence was reduced by 4.96% after surgery for DS. Prior opioid dependence is associated with increased risk and increasing age is associated with decreased risk of opioid dependence following surgery for DS.

OBJECTIVE: Cognitive dysfunction occurs in up to 70% of aneurysmal subarachnoid hemorrhage (aSAH) survivors. Low-dose intravenous heparin (LDIVH) infusion using the Maryland protocol was recently shown to reduce clinical vasospasm and vasospasm-related infarction. In this study, the Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive changes in aSAH patients treated with the Maryland LDIVH protocol compared with controls.METHODS: A retrospective analysis of all patients treated for aSAH between July 2009 and April 2014 was conducted. Beginning in 2012, aSAH patients were treated with LDIVH in the postprocedural period. The MoCA was administered to all aSAH survivors prospectively during routine follow-up visits, at least 3 months after aSAH, by trained staff blinded to treatment status. Mean MoCA scores were compared between groups, and regression analyses were performed for relevant factors.RESULTS: No significant differences in baseline characteristics were observed between groups. The mean MoCA score for the LDIVH group (n = 25) was 26.4 compared with 22.7 in controls (n = 22) (p = 0.013). Serious cognitive impairment (MoCA ≤ 20) was observed in 32% of controls compared with 0% in the LDIVH group (p = 0.008). Linear regression analysis demonstrated that only LDIVH was associated with a positive influence on MoCA scores (β = 3.68, p =0.019), whereas anterior communicating artery aneurysms and fevers were negatively associated with MoCA scores. Multivariable linear regression analysis resulted in all 3 factors maintaining significance. There were no treatment complications.CONCLUSIONS: This preliminary study suggests that the Maryland LDIVH protocol may improve cognitive outcomes in aSAH patients. A randomized controlled trial is needed to determine the safety and potential benefit of unfractionated heparin in aSAH patients.