Sergiu Albu1, Hatice Kumru2, Ruth Coll3, Joaquim Vives4, Margarita Vallés1, Jesús Benito-Penalva1, Luciano Rodríguez4, Margarita Codinach5, Joaquim Hernández6, Xavier Navarro7, Joan Vidal1. 1. Fundación Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Hospital de Neurorehabilitació, Barcelona, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain; Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Barcelona, Spain. 2. Fundación Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Hospital de Neurorehabilitació, Barcelona, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain; Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Barcelona, Spain. Electronic address: hkumru@guttmann.com. 3. Research and Education, Banc de Sang i Teixits, Barcelona, Spain. 4. Cell Therapy Service, Banc de Sang i Teixits, Barcelona, Spain. 5. Cellular Laboratory, Banc de Sang i Teixits, Barcelona, Spain. 6. Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain. 7. Fundación Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Hospital de Neurorehabilitació, Barcelona, Spain; Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain.
Abstract
BACKGROUND AIMS: Spinal cord injury (SCI) represents a devastating condition leading to severe disability related to motor, sensory and autonomic dysfunction. Stem cell transplantation is considered a potential emerging therapy to stimulate neuroplastic and neuroregenerative processes after SCI. In this clinical trial, the authors investigated the safety and clinical recovery effects of intrathecal infusion of expanded Wharton jelly mesenchymal stromal cells (WJ-MSCs) in chronic complete SCI patients. METHODS: The authors designed a randomized, double-blind, crossover, placebo-controlled, phase 1/2a clinical trial (NCT03003364). Participants were 10 patients (7 males, 3 females, age range, 25-47 years) with chronic complete SCI (American Spinal Injury Association A) at dorsal level (T3-11). Patients were randomly assigned to receive a single dose of intrathecal ex vivo-expanded WJ-MSCs (10 × 106 cells) from human umbilical cord or placebo and were then switched to the other arm at 6 months. Clinical evaluation (American Spinal Injury Association impairment scale motor and sensory score, spasticity, neuropathic pain, electrical perception and pain thresholds), lower limb motor evoked potentials (MEPs) and sensory evoked potentials (SEPs), Spinal Cord Independence Measure and World Health Organization Quality of Life Brief Version were assessed at baseline, 1 month, 3 months and 6 months after each intervention. Urodynamic studies and urinary-specific quality of life (Qualiveen questionnaire) as well as anorectal manometry, functional assessment of bowel dysfunction (Rome III diagnostic questionnaire) and severity of fecal incontinence (Wexner score) were conducted at baseline and at 6 months after each intervention. RESULTS: Intrathecal transplantation of WJ-MSCs was considered safe, with no significant side effects. Following MSC infusion, the authors found significant improvement in pinprick sensation in the dermatomes below the level of injury compared with placebo. Other clinically relevant effects, such as an increase in bladder maximum capacity and compliance and a decrease in bladder neurogenic hyperactivity and external sphincter dyssynergy, were observed only at the individual level. No changes in motor function, spasticity, MEPs, SEPs, bowel function, quality of life or independence measures were observed. CONCLUSIONS:Intrathecal transplantation of human umbilical cord-derived WJ-MSCs is a safe intervention. A single intrathecal infusion of WJ-MSCs in patients with chronic complete SCI induced sensory improvement in the segments adjacent to the injury site.
RCT Entities:
BACKGROUND AIMS: Spinal cord injury (SCI) represents a devastating condition leading to severe disability related to motor, sensory and autonomic dysfunction. Stem cell transplantation is considered a potential emerging therapy to stimulate neuroplastic and neuroregenerative processes after SCI. In this clinical trial, the authors investigated the safety and clinical recovery effects of intrathecal infusion of expanded Wharton jelly mesenchymal stromal cells (WJ-MSCs) in chronic complete SCI patients. METHODS: The authors designed a randomized, double-blind, crossover, placebo-controlled, phase 1/2a clinical trial (NCT03003364). Participants were 10 patients (7 males, 3 females, age range, 25-47 years) with chronic complete SCI (American Spinal Injury Association A) at dorsal level (T3-11). Patients were randomly assigned to receive a single dose of intrathecal ex vivo-expanded WJ-MSCs (10 × 106 cells) from human umbilical cord or placebo and were then switched to the other arm at 6 months. Clinical evaluation (American Spinal Injury Association impairment scale motor and sensory score, spasticity, neuropathic pain, electrical perception and pain thresholds), lower limb motor evoked potentials (MEPs) and sensory evoked potentials (SEPs), Spinal Cord Independence Measure and World Health Organization Quality of Life Brief Version were assessed at baseline, 1 month, 3 months and 6 months after each intervention. Urodynamic studies and urinary-specific quality of life (Qualiveen questionnaire) as well as anorectal manometry, functional assessment of bowel dysfunction (Rome III diagnostic questionnaire) and severity of fecal incontinence (Wexner score) were conducted at baseline and at 6 months after each intervention. RESULTS: Intrathecal transplantation of WJ-MSCs was considered safe, with no significant side effects. Following MSC infusion, the authors found significant improvement in pinprick sensation in the dermatomes below the level of injury compared with placebo. Other clinically relevant effects, such as an increase in bladder maximum capacity and compliance and a decrease in bladder neurogenic hyperactivity and external sphincter dyssynergy, were observed only at the individual level. No changes in motor function, spasticity, MEPs, SEPs, bowel function, quality of life or independence measures were observed. CONCLUSIONS: Intrathecal transplantation of human umbilical cord-derived WJ-MSCs is a safe intervention. A single intrathecal infusion of WJ-MSCs in patients with chronic complete SCI induced sensory improvement in the segments adjacent to the injury site.
Authors: Emmanouil I Damianakis; Ioannis S Benetos; Dimitrios Stergios Evangelopoulos; Aikaterini Kotroni; John Vlamis; Spyridon G Pneumaticos Journal: Cureus Date: 2022-04-28
Authors: Christopher Elnan Kvistad; Torbjørn Kråkenes; Cecilie Gjerde; Kamal Mustafa; Tiina Rekand; Lars Bø Journal: Front Neurol Date: 2022-05-30 Impact factor: 4.086