BMC Neurology (Mar 2022)
The safety and efficacy of umbilical cord blood mononuclear cells in individuals with spastic cerebral palsy: a randomized double-blind sham-controlled clinical trial
- Morteza Zarrabi,
- Masood Ghahvechi Akbari,
- Man Amanat,
- Anahita Majmaa,
- Ali Reza Moaiedi,
- Hadi Montazerlotfelahi,
- Masoumeh Nouri,
- Amir Ali Hamidieh,
- Reza Shervin Badv,
- Hossein Karimi,
- Ali Rabbani,
- Ali Mohebbi,
- Shahram Rahimi-Dehgolan,
- Rosa Rahimi,
- Ensieh Dehghan,
- Massoud Vosough,
- Saeed Abroun,
- Farhad Mahvelati Shamsabadi,
- Ali Reza Tavasoli,
- Houman Alizadeh,
- Neda Pak,
- Gholam Reza Zamani,
- Mahmoud Mohammadi,
- Mohsen Javadzadeh,
- Mohammad Ghofrani,
- Seyed Hossein Hassanpour,
- Morteza Heidari,
- Mohammad Mehdi Taghdiri,
- Mohamad Javad Mohseni,
- Zahra Noparast,
- Safdar Masoomi,
- Mehrdad Goudarzi,
- Masood Mohamadpour,
- Razieh Shodjaee,
- Solaleh Samimi,
- Monireh Mohammad,
- Mona Gholami,
- Nahid Vafaei,
- Leyli Koochakzadeh,
- Amir Valizadeh,
- Reza Azizi Malamiri,
- Mahmoud Reza Ashrafi
Affiliations
- Morteza Zarrabi
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR
- Masood Ghahvechi Akbari
- Physical Medicine and Rehabilitation Department, Children’s Medical Center, Tehran University of Medical Sciences
- Man Amanat
- Division of Neurogenetics and Neuroscience, The Moser Center for Leukodystrophies, Kennedy Krieger Institute, Johns Hopkins University
- Anahita Majmaa
- Pediatrics Center of Excellence, Pediatric Intensive Unit, Children’s Medical Center, Tehran University of Medical Sciences
- Ali Reza Moaiedi
- Department of Pediatric Neurology, Clinical Research Development Center of Children Hospital, Hormozgan University of Medical Sciences
- Hadi Montazerlotfelahi
- Department of Pediatrics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University
- Masoumeh Nouri
- R & D Department, Royan Stem Cell Technology Co
- Amir Ali Hamidieh
- Pediatrics Center of Excellence Pediatric Hematology, Oncology and Stem Cell Transplantation Department, Children’s Medical Center, Tehran University of Medical Sciences
- Reza Shervin Badv
- Pediatrics Center of Excellence, Department of Pediatric Neurology, Children’s Medical Center, Growth and Development Research Center, Tehran University of Medical Sciences
- Hossein Karimi
- Neurorehabilitation Research Center University of Welfare and Rehabilitation Sciences
- Ali Rabbani
- Pediatrics Center of Excellence Pediatric Endocrinology Department, Growth and Development Research Center, Children’s Medical Center, Tehran University of Medical Sciences
- Ali Mohebbi
- Pediatrics Center of Excellence, Growth and Development Research Center, Children’s Medical Center, Tehran University of Medical Sciences
- Shahram Rahimi-Dehgolan
- Physical Medicine and Rehabilitation Department, Tehran University of Medical Sciences
- Rosa Rahimi
- Physical Medicine and Rehabilitation Department, Khatamolanbia Hospital
- Ensieh Dehghan
- Transplantation Department, Royan Stem Cell Technology Co
- Massoud Vosough
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR
- Saeed Abroun
- Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University
- Farhad Mahvelati Shamsabadi
- Department of Pediatric Neurology, Atieh Hospital
- Ali Reza Tavasoli
- Pediatrics Center of Excellence, Department of Pediatric Neurology, Children’s Medical Center, Growth and Development Research Center, Tehran University of Medical Sciences
- Houman Alizadeh
- Pediatrics Center of Excellence, Department of Radiology, Children’s Medical Center, Tehran University of Medical Sciences
- Neda Pak
- Pediatrics Center of Excellence, Department of Radiology, Children’s Medical Center, Tehran University of Medical Sciences
- Gholam Reza Zamani
- Pediatrics Center of Excellence, Department of Pediatric Neurology, Children’s Medical Center, Growth and Development Research Center, Tehran University of Medical Sciences
- Mahmoud Mohammadi
- Pediatrics Center of Excellence, Department of Pediatric Neurology, Children’s Medical Center, Growth and Development Research Center, Tehran University of Medical Sciences
- Mohsen Javadzadeh
- Department of Pediatric Neurology, Mofid Children’s Hospital, Pediatric Neurology Research Center, Shahid Beheshti University of Medical Sciences
- Mohammad Ghofrani
- Department of Pediatric Neurology, Mofid Children’s Hospital, Pediatric Neurology Research Center, Shahid Beheshti University of Medical Sciences
- Seyed Hossein Hassanpour
- Department of Pediatric Neurology, Aliasghar Children’s Hospital, Iran University of Medical Sciences
- Morteza Heidari
- Pediatrics Center of Excellence, Department of Pediatric Neurology, Children’s Medical Center, Growth and Development Research Center, Tehran University of Medical Sciences
- Mohammad Mehdi Taghdiri
- Department of Pediatric Neurology, Mofid Children’s Hospital, Pediatric Neurology Research Center, Shahid Beheshti University of Medical Sciences
- Mohamad Javad Mohseni
- Pediatric Urology Research Center, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences
- Zahra Noparast
- Department of Pediatric Nephrology, Bahrami Hospital, Tehran University of Medical Sciences
- Safdar Masoomi
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences
- Mehrdad Goudarzi
- Department of Pediatric Anesthesiology, Children’s Medical Center, Tehran University of Medical Sciences
- Masood Mohamadpour
- Pediatrics Center of Excellence, Pediatric Intensive Unit, Children’s Medical Center, Tehran University of Medical Sciences
- Razieh Shodjaee
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR
- Solaleh Samimi
- Physical Medicine and Rehabilitation Department, Khatamolanbia Hospital
- Monireh Mohammad
- Process Department, Royan Stem Cell Technology Co
- Mona Gholami
- Physical Medicine and Rehabilitation Department, Khatamolanbia Hospital
- Nahid Vafaei
- Faculty of Medicine, Students’ Scientific Research Center, Tehran University of Medical Sciences
- Leyli Koochakzadeh
- Pediatrics Center of Excellence Pediatric Hematology, Department of Hematology & Oncology, Children’s Medical Center, Tehran University of Medical Sciences
- Amir Valizadeh
- Faculty of Medicine, Students’ Scientific Research Center, Tehran University of Medical Sciences
- Reza Azizi Malamiri
- Department of Paediatric Neurology, Golestan Medical, Educational, and Research Center, Ahvaz Jundishapur University of Medical Sciences
- Mahmoud Reza Ashrafi
- Pediatrics Center of Excellence, Department of Pediatric Neurology, Children’s Medical Center, Growth and Development Research Center, Tehran University of Medical Sciences
- DOI
- https://doi.org/10.1186/s12883-022-02636-y
- Journal volume & issue
-
Vol. 22,
no. 1
pp. 1 – 13
Abstract
Abstract Introduction The current multi-center, randomized, double-blind study was conducted among children with cerebral palsy (CP) to assess the safety and efficacy of umbilical cord blood mononuclear cell (UCB-MNC). We performed the diffusion tensor imaging to assess the changes in the white matter structure. Methods Males and females aged 4 to 14 years old with spastic CP were included. Eligible participants were allocated in 4:1 ratio to be in the experimental or control groups; respectively. Individuals who were assigned in UCB-MNC group were tested for human leukocyte antigen (HLA) and fully-matched individuals were treated with UCB-MNCs. A single dose (5 × 106 /kg) UCB-MNCs were administered via intrathecal route in experimental group. The changes in gross motor function measure (GMFM)-66 from baseline to one year after treatment were the primary endpoints. The mean changes in modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also evaluated and compared between groups. The mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR) were the secondary endpoints. Adverse events were safety endpoint. Results There were 72 included individuals (36 cases in each group). The mean GMFM-66 scores increased in experimental group; compared to baseline (+ 9.62; 95%CI: 6.75, 12.49) and control arm (β: 7.10; 95%CI: 2.08, 12.76; Cohen’s d: 0.62) and mean MAS reduced in individuals treated with UCB-MNCs compared to the baseline (-0.87; 95%CI: -1.2, -0.54) and control group (β: -0.58; 95%CI: -1.18, -0.11; Cohen’s d: 0.36). The mean PEDI scores and mean CP-QoL scores in two domains were higher in the experimental group compared to the control. The imaging data indicated that mean FA increased and MD decreased in participants of UCB-MNC group indicating improvements in white matter structure. Lower back pain, headaches, and irritability were the most common adverse events within 24 h of treatment that were related to lumbar puncture. No side effects were observed during follow-up. Conclusions This trial showed that intrathecal injection of UCB-MNCs were safe and effective in children with CP. Trial Registration The study was registered with ClinicalTrials.gov ( NCT03795974 ).
Keywords
