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Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial.

ABSTRACT: Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study's primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI.

SUBMITTER: Bydon M

PROVIDER: S-EPMC10984970 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial.

Bydon Mohamad M Qu Wenchun W Moinuddin F M FM Hunt Christine L CL Garlanger Kristin L KL Reeves Ronald K RK Windebank Anthony J AJ Zhao Kristin D KD Jarrah Ryan R Trammell Brandon C BC El Sammak Sally S Michalopoulos Giorgos D GD Katsos Konstantinos K Graepel Stephen P SP Seidel-Miller Kimberly L KL Beck Lisa A LA Laughlin Ruple S RS Dietz Allan B AB

Nature communications 20240401 1

Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study's primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory ...[more]

PMID: 38561341

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Project description:BackgroundCell-based therapy using adipose-derived mesenchymal stem cells (ADSCs) is a promising treatment strategy for neurogenic bladder (NB) associated with spinal cord injury (SCI). However, therapeutic efficacy is low because of inefficient cell delivery. Cell sheets improve the efficacy of cell transplantation. Therefore, this study was conducted to investigate the therapeutic efficacy of transplanting ADSC sheets into an SCI rat model and focused on the function and pathological changes of the bladder.MethodsADSC sheets were prepared from adipose tissue of Sprague-Dawley (SD) rats using temperature-responsive cell culture dishes. Adult female SD rats were subjected to SCI by transection at the T10 level and administered ADSC sheets or gelatin sponge (the control group). Four and 8 weeks later, in vivo cystometrograms were obtained for voiding function assessment. Rats were sacrificed and the expression of various markers was analyzed in spinal and bladder tissues.ResultsThe number of β-tubulin III-positive axons in the ADSC sheet transplantation group was higher than that in the control group. Conversely, expression of glial fibrillary acidic protein in the ADSC sheet transplantation group was lower than that in the control group. Cystometry showed impairment of the voiding function after SCI, which was improved after ADSC sheet transplantation with increased high-frequency oscillation activity. Furthermore, ADSC sheet transplantation prevented disruption of the bladder urothelium in SCI rats, thereby maintaining the intact barrier. Compared with fibrosis of the bladder wall in the control group, the ADSC sheet transplantation group had normal morphology of the bladder wall and reduced tissue fibrosis as shown by downregulation of type 1 collagen. ADSC sheet transplantation also resulted in strong upregulation of contractile smooth muscle cell (SMC) markers (α-smooth muscle actin and smoothelin) and downregulation of synthetic SMC markers (MYH10 and RBP1).ConclusionADSC sheet transplantation significantly improved voiding function recovery in rats after SCI. ADSC sheet transplantation is a promising cell delivery and treatment option for NB related to SCI.

Project description:ObjectiveNeurological 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.MethodsThis 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.ResultsNine 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.ConclusionsThis 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 registrationIranian Registry of Clinical Trials, IRCT20200502047277N1. Registered 2 October 2020, https://en.irct.ir/trial/48765 .

Dataset Information

Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial.

Publications

Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial.

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