Safety and potential effects of intrathecal injection of allogeneic human umbilical cord mesenchymal stem cell-derived exosomes in complete subacute spinal cord injury: a first-in-human, single-arm, open-label, phase I clinical trial.

OBJECTIVE: Neurological and functional impairments are commonly observed in individuals with spinal cord injury (SCI) due to insufficient regeneration of damaged axons. Exosomes play a crucial role in the paracrine effects of mesenchymal stem cells (MSCs) and have emerged as a promising therapeutic approach for SCI. Thus, this study aimed to evaluate the safety and potential effects of intrathecal administration of allogeneic exosomes derived from human umbilical cord MSCs (HUC-MSCs) in patients with complete subacute SCI. METHODS: This study was a single-arm, open-label, phase I clinical trial with a 12-month follow-up period. HUC-MSCs were extracted from human umbilical cord tissue, and exosomes were isolated via ultracentrifugation. After intrathecal injection, each participant a underwent complete evaluation, including neurological assessment using the American Spinal Injury Association (ASIA) scale, functional assessment using the Spinal Cord Independence Measure (SCIM-III), neurogenic bowel dysfunction (NBD) assessment using the NBD score, modified Ashworth scale (MAS), and lower urinary tract function questionnaire. RESULTS: Nine patients with complete subacute SCI were recruited. The intrathecal injection of allogeneic HUC-MSCs-exosomes was safe and well tolerated. No early or late adverse event (AE) attributable to the study intervention was observed. Significant improvements in ASIA pinprick (P-value = 0.039) and light touch (P-value = 0.038) scores, SCIM III total score (P-value = 0.027), and NBD score (P-value = 0.042) were also observed at 12-month after the injection compared with baseline. CONCLUSIONS: This study demonstrated that intrathecal administration of allogeneic HUC-MSCs-exosomes is safe in patients with subacute SCI. Moreover, it seems that this therapy might be associated with potential clinical and functional improvements in these patients. In this regard, future larger phase II/III clinical trials with adequate power are highly required. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT20200502047277N1. Registered 2 October 2020, https://en.irct.ir/trial/48765 .

Epidemiology of malignant gliomas in Iran: first report of Iranian National Population-based Cancer Registry, 2009-2017.

OBJECTIVE: Malignant gliomas constitute the most common type of primary malignant brain tumors. Most previous studies have evaluated the epidemiology of malignant gliomas in developed countries. Hence, there is a lack of evidence in this regard from developing countries. This study is the first epidemiological report on the status of malignant glioma in Iran between 2009 and 2017. METHODS: Data from the Iranian National Population-based Cancer Registry (covering 98% of the Iranian population) on CNS tumors recorded from 2009 to 2017 were used for analysis. Age-adjusted incidence rates were calculated by sex, tumor histology, tumor site, and year of diagnosis. Trend analysis of incidence rates was also performed. Survival data were recorded and the Cox proportional hazards model was used to evaluate underlying risk factors. RESULTS: A total of 8484 patients were diagnosed with malignant glioma between 2009 and 2017 in Iran. The overall age-adjusted incidence rate of malignant gliomas over the 9-year period was 1.71 per 100,000 persons. The most common histology of malignant gliomas was glioblastoma (81.4%). A significant increase in the incidence of malignant gliomas was found between 2009 and 2012. The median overall survival was 13.0 (95% CI 12.6-13.5) months over the study period. Older age groups, higher tumor grade, male sex, the first half of the study period, and receiving no treatment were significantly associated with worse prognoses. CONCLUSIONS: This study is the latest epidemiological report on the status of malignant gliomas in Iran. Although the overall incidence rate was lower than the rates in developed countries, several findings were consistent with those in prior reports.