Man Amanat1, Anahita Majmaa2, Morteza Zarrabi3, Masoumeh Nouri3, Masood Ghahvechi Akbari2, Ali Reza Moaiedi4, Omid Ghaemi5, Fatemeh Zamani5, Sharif Najafi6, Reza Shervin Badv2, Massoud Vosough3, Amir Ali Hamidieh7, Mona Salehi8, Hadi Montazerlotfelahi9, Ali Reza Tavasoli2, Morteza Heidari2, Hossein Mohebi10, Ali Fatemi11,12, Amir Garakani13,14, Mahmoud Reza Ashrafi15. 1. Department of Science and Research Branch, AJA University of Medical Sciences, Tehran, Iran. 2. Pediatrics Center of Excellence, Department of Pediatric Neurology, Children's Medical Center, Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. 3. Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. 4. Department of Pediatric Neurology, Clinical Research Development Center of Children Hospital, Hormozgan University of Medical Sciences, Bandar Abass, Iran. 5. Pediatrics Center of Excellence, Department of Radiology, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 6. Clinical Biomechanics and Ergonomics Research Center, Department of Physical Medicine and Rehabilitation, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran. 7. Pediatrics Center of Excellence Pediatric Hematology, Oncology and Stem Cell Transplantation Department, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 8. Psychiatry and Psychology Research Center, Tehran University of Medical Sciences, Tehran, Iran. 9. Department of Pediatrics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 10. Department of Pediatric Neurology, AJA University of Medical Sciences, Tehran, Iran. 11. Moser Center for Leukodystrophies, Kennedy Krieger Institute, Baltimore, MD, 21205, USA. 12. Department of Neurology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. 13. Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA. 14. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 15. Pediatrics Center of Excellence, Department of Pediatric Neurology, Children's Medical Center, Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. ashrafim@tums.ac.ir.
Abstract
BACKGROUND: This study assessed the safety and efficacy of intrathecal injection of umbilical cord tissue mesenchymal stem cells (UCT-MSC) in individuals with cerebral palsy (CP). The diffusion tensor imaging (DTI) was performed to evaluate the alterations in white-matter integrity. METHODS:Participants (4-14 years old) with spastic CP were assigned in 1:1 ratio to receive either UCT-MSC or sham procedure. Single-dose (2 × 107) cells were administered in the experimental group. Small needle pricks to the lower back were performed in the sham-control arm. All individuals were sedated to prevent awareness. The primary endpoints were the mean changes in gross motor function measure (GMFM)-66 from baseline to 12 months after procedures. The mean changes in the modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also assessed. Secondary endpoints were the mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR). RESULTS: There were 36 participants in each group. The mean GMFM-66 scores after 12 months of intervention were significantly higher in the UCT-MSC group compared to baseline (10.65; 95%CI 5.39, 15.91) and control (β 8.07; 95%CI 1.62, 14.52; Cohen's d 0.92). The increase was also seen in total PEDI scores (vs baseline 8.53; 95%CI 4.98, 12.08; vs control: β 6.87; 95%CI 1.52, 12.21; Cohen's d 0.70). The mean change in MAS scores after 12 months of cell injection reduced compared to baseline (-1.0; 95%CI -1.31, -0.69) and control (β -0.72; 95%CI -1.18, -0.26; Cohen's d 0.76). Regarding CP-QoL, mean changes in domains including friends and family, participation in activities, and communication were higher than the control group with a large effect size. The DTI analysis in the experimental group showed that mean FA increased (CST 0.032; 95%CI 0.02, 0.03. PTR 0.024; 95%CI 0.020, 0.028) and MD decreased (CST -0.035 × 10-3; 95%CI -0.04 × 10-3, -0.02 × 10-3. PTR -0.045 × 10-3; 95%CI -0.05 × 10-3, -0.03 × 10-3); compared to baseline. The mean changes were significantly higher than the control group. CONCLUSIONS: The UCT-MSC transplantation was safe and may improve the clinical and imaging outcomes. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ( NCT03795974 ).
RCT Entities:
BACKGROUND: This study assessed the safety and efficacy of intrathecal injection of umbilical cord tissue mesenchymal stem cells (UCT-MSC) in individuals with cerebral palsy (CP). The diffusion tensor imaging (DTI) was performed to evaluate the alterations in white-matter integrity. METHODS:Participants (4-14 years old) with spastic CP were assigned in 1:1 ratio to receive either UCT-MSC or sham procedure. Single-dose (2 × 107) cells were administered in the experimental group. Small needle pricks to the lower back were performed in the sham-control arm. All individuals were sedated to prevent awareness. The primary endpoints were the mean changes in gross motor function measure (GMFM)-66 from baseline to 12 months after procedures. The mean changes in the modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also assessed. Secondary endpoints were the mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR). RESULTS: There were 36 participants in each group. The mean GMFM-66 scores after 12 months of intervention were significantly higher in the UCT-MSC group compared to baseline (10.65; 95%CI 5.39, 15.91) and control (β 8.07; 95%CI 1.62, 14.52; Cohen's d 0.92). The increase was also seen in total PEDI scores (vs baseline 8.53; 95%CI 4.98, 12.08; vs control: β 6.87; 95%CI 1.52, 12.21; Cohen's d 0.70). The mean change in MAS scores after 12 months of cell injection reduced compared to baseline (-1.0; 95%CI -1.31, -0.69) and control (β -0.72; 95%CI -1.18, -0.26; Cohen's d 0.76). Regarding CP-QoL, mean changes in domains including friends and family, participation in activities, and communication were higher than the control group with a large effect size. The DTI analysis in the experimental group showed that mean FA increased (CST 0.032; 95%CI 0.02, 0.03. PTR 0.024; 95%CI 0.020, 0.028) and MD decreased (CST -0.035 × 10-3; 95%CI -0.04 × 10-3, -0.02 × 10-3. PTR -0.045 × 10-3; 95%CI -0.05 × 10-3, -0.03 × 10-3); compared to baseline. The mean changes were significantly higher than the control group. CONCLUSIONS: The UCT-MSC transplantation was safe and may improve the clinical and imaging outcomes. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ( NCT03795974 ).
Authors: Peter L Rosenbaum; Robert J Palisano; Doreen J Bartlett; Barbara E Galuppi; Dianne J Russell Journal: Dev Med Child Neurol Date: 2008-03-01 Impact factor: 5.449
Authors: E Gluckman; H A Broxmeyer; A D Auerbach; H S Friedman; G W Douglas; A Devergie; H Esperou; D Thierry; G Socie; P Lehn Journal: N Engl J Med Date: 1989-10-26 Impact factor: 91.245
Authors: Iona Novak; Karen Walker; Rod W Hunt; Euan M Wallace; Michael Fahey; Nadia Badawi Journal: Stem Cells Transl Med Date: 2016-05-31 Impact factor: 6.940