Clinical and imaging outcomes after intrathecal injection of umbilical cord tissue mesenchymal stem cells in cerebral palsy: a randomized double-blind sham-controlled clinical trial

Man Amanat; Anahita Majmaa; Morteza Zarrabi; Masoumeh Nouri; Masood Ghahvechi Akbari; Ali Reza Moaiedi; Omid Ghaemi; Fatemeh Zamani; Sharif Najafi; Reza Shervin Badv; Massoud Vosough; Amir Ali Hamidieh; Mona Salehi; Hadi Montazerlotfelahi; Ali Reza Tavasoli; Morteza Heidari; Hossein Mohebi; Ali Fatemi; Amir Garakani; Mahmoud Reza Ashrafi

doi:10.1186/s13287-021-02513-4

Clinical and imaging outcomes after intrathecal injection of umbilical cord tissue mesenchymal stem cells in cerebral palsy: a randomized double-blind sham-controlled clinical trial

Stem Cell Res Ther. 2021 Aug 6;12(1):439. doi: 10.1186/s13287-021-02513-4.

Authors

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 Fatemi^{11

12}, Amir Garakani^{13

14}, Mahmoud Reza Ashrafi¹⁵

Affiliations

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 ).

Keywords: Cerebral palsy; Children; Diffusion tensor imaging; Gross motor function; Stem cell.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Cerebral Palsy* / diagnostic imaging
Cerebral Palsy* / therapy
Child
Child, Preschool
Diffusion Tensor Imaging
Humans
Injections, Spinal
Mesenchymal Stem Cells*
Quality of Life
Umbilical Cord / diagnostic imaging

Associated data

ClinicalTrials.gov/NCT03795974