Mechanisms of Stem Cell Therapy in Spinal Cord Injuries.

Every year, 0.93 million people worldwide suffer from spinal cord injury (SCI) with irretrievable sequelae. Rehabilitation, currently the only available treatment, does not restore damaged tissues; therefore, the functional recovery of patients remains limited. The pathophysiology of spinal cord injuries is heterogeneous, implying that potential therapeutic targets differ depending on the time of injury onset, the degree of injury, or the spinal level of injury. In recent years, despite a significant number of clinical trials based on various types of stem cells, these aspects of injury have not been effectively considered, resulting in difficult outcomes of trials. In a specialty such as cancerology, precision medicine based on a patient's characteristics has brought indisputable therapeutic advances. The objective of the present review is to promote the development of precision medicine in the field of SCI. Here, we first describe the multifaceted pathophysiology of SCI, with the temporal changes after injury, the characteristics of the chronic phase, and the subtypes of complete injury. We then detail the appropriate targets and related mechanisms of the different types of stem cell therapy for each pathological condition. Finally, we highlight the great potential of stem cell therapy in cervical SCI.

Predictive model for major complications 2 years after corrective spine surgery for adult spinal deformity.

PURPOSE: ASD surgery improves a patient's health-related quality of life, but it has a high complication rate. The aim of this study was to create a predictive model for complications after surgical treatment for adult spinal deformity (ASD), using spinal alignment, demographic data, and surgical invasiveness. METHODS: This study included 195 surgically treated ASD patients who were > 50 years old and had 2-year follow-up from multicenter database. Variables which included age, gender, BMI, BMD, frailty, fusion level, UIV and LIV, primary or revision surgery, pedicle subtraction osteotomy, spinal alignment, Schwab-SRS type, surgical time, and blood loss were recorded and analyzed at least 2 years after surgery. Decision-making trees for 2-year postoperative complications were constructed and validated by a 7:3 data split for training and testing. External validation was performed for 25 ASD patients who had surgery at a different hospital. RESULTS: Complications developed in 48% of the training samples. Almost half of the complications developed in late post-op period, and implant-related complications were the most common complication at 2 years after surgery. Univariate analyses showed that BMD, frailty, PSO, LIV, PI-LL, and EBL were risk factors for complications. Multivariate analysis showed that low BMD, PI-LL > 30°, and frailty were independent risk factors for complications. In the testing samples, our predictive model was 92% accurate with an area under the receiver operating characteristic curve of 0.963 and 84% accurate in the external validation. CONCLUSION: A successful model was developed for predicting surgical complications. Our model could inform physicians about the risk of complications in ASD patients in the 2-year postoperative period. These slides can be retrieved under Electronic Supplementary Material.

Investigational drugs for the treatment of spinal cord injury: review of preclinical studies and evaluation of clinical trials from Phase I to II.

INTRODUCTION: Efforts in basic research have clarified mechanisms involved in spinal cord injury (SCI), and resulted in positive findings using experimental treatments including cell transplantation and drug administration preclinically. Based on accumulated results, various clinical trials have begun for human SCI. AREAS COVERED: In this review, the authors focus on five investigational drugs: riluzole, minocycline, Rho protein antagonist, magnesium chloride in polyethylene glycol formulation, and basic fibroblast growth factor. All drugs have established safety and tolerability from Phase I clinical trials, and are now in Phase II. They have been proven to have neuroprotective and/or neuroregenerative effects in animal models of SCI. EXPERT OPINION: To date, diverse drugs have been translated into clinical trials, but none have reached clinical application. A key gap was the lack of reliable biomarkers for SCI to fast-track Phase I/II trials. Furthermore, problems were often due to lack of adequate outcome assessments for both animal models and SCI patients. In order to advance clinical trials more quickly and with greater success, more clinically relevant animal models should be used in basic research. Clinically, it is indispensable to use appropriate outcome measurements and to construct a wide network among clinical centers to validate the efficacy of drugs.