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The Safety and Efficacy of Umbilical Cord Blood Mononuclear Cells in Individuals With Spastic Cerebral Palsy: A Randomized Double-Blind Sham-Controlled Clinical Trial Publisher Pubmed



Zarrabi M1 ; Akbari MG2 ; Amanat M3 ; Majmaa A4 ; Moaiedi AR5 ; Montazerlotfelahi H6 ; Nouri M7 ; Hamidieh AA8 ; Badv RS9 ; Karimi H10 ; Rabbani A11 ; Mohebbi A12 ; Rahimidehgolan S13 ; Rahimi R14 Show All Authors
Authors
  1. Zarrabi M1
  2. Akbari MG2
  3. Amanat M3
  4. Majmaa A4
  5. Moaiedi AR5
  6. Montazerlotfelahi H6
  7. Nouri M7
  8. Hamidieh AA8
  9. Badv RS9
  10. Karimi H10
  11. Rabbani A11
  12. Mohebbi A12
  13. Rahimidehgolan S13
  14. Rahimi R14
  15. Dehghan E15
  16. Vosough M1
  17. Abroun S16
  18. Shamsabadi FM17
  19. Tavasoli AR9
  20. Alizadeh H18
  21. Pak N18
  22. Zamani GR9
  23. Mohammadi M9
  24. Javadzadeh M19
  25. Ghofrani M19
  26. Hassanpour SH20
  27. Heidari M9
  28. Taghdiri MM19
  29. Mohseni MJ21
  30. Noparast Z22
  31. Masoomi S23
  32. Goudarzi M24
  33. Mohamadpour M4
  34. Shodjaee R1
  35. Samimi S14
  36. Mohammad M25
  37. Gholami M14
  38. Vafaei N26
  39. Koochakzadeh L27
  40. Valizadeh A26
  41. Malamiri RA28
  42. Ashrafi MR9
Show Affiliations
Authors Affiliations
  1. 1. Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  2. 2. Physical Medicine and Rehabilitation Department, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Division of Neurogenetics and Neuroscience, The Moser Center for Leukodystrophies, Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD, United States
  4. 4. Pediatrics Center of Excellence, Pediatric Intensive Unit, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Pediatric Neurology, Clinical Research Development Center of Children Hospital, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
  6. 6. Department of Pediatrics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  7. 7. R & D Department, Royan Stem Cell Technology Co, Tehran, Iran
  8. 8. Pediatrics Center of Excellence Pediatric Hematology, Oncology and Stem Cell Transplantation Department, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Pediatrics Center of Excellence, Department of Pediatric Neurology, Children’s Medical Center, Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Neurorehabilitation Research Center University of Welfare and Rehabilitation Sciences, Tehran, Iran
  11. 11. Pediatrics Center of Excellence Pediatric Endocrinology Department, Growth and Development Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  12. 12. Pediatrics Center of Excellence, Growth and Development Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  13. 13. Physical Medicine and Rehabilitation Department, Tehran University of Medical Sciences, Tehran, Iran
  14. 14. Physical Medicine and Rehabilitation Department, Khatamolanbia Hospital, Tehran, Iran
  15. 15. Transplantation Department, Royan Stem Cell Technology Co, Tehran, Iran
  16. 16. Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  17. 17. Department of Pediatric Neurology, Atieh Hospital, Tehran, Iran
  18. 18. Pediatrics Center of Excellence, Department of Radiology, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  19. 19. Department of Pediatric Neurology, Mofid Children’s Hospital, Pediatric Neurology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  20. 20. Department of Pediatric Neurology, Aliasghar Children’s Hospital, Iran University of Medical Sciences, Tehran, Iran
  21. 21. Pediatric Urology Research Center, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  22. 22. Department of Pediatric Nephrology, Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran
  23. 23. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  24. 24. Department of Pediatric Anesthesiology, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  25. 25. Process Department, Royan Stem Cell Technology Co, Tehran, Iran
  26. 26. Faculty of Medicine, Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
  27. 27. Pediatrics Center of Excellence Pediatric Hematology, Department of Hematology & Oncology, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  28. 28. Department of Paediatric Neurology, Golestan Medical, Educational, and Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Source: BMC Neurology Published:2022


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). © 2022, The Author(s).