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, 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

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.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
The ROI-based tractography of the corticospinal tract and posterior thalamic radiation
Fig. 2
Fig. 2
The flow cytometry analysis of UCT-MSC-specific markers. The first three photos (a, b, c) shows the cell gating to select single live UCT-MSCs. Othe photos (d-l) shows that the cells were negative for CD11b, CD31, CD34, CD45, and HLA-DR and were positive for CD29, CD73, CD90, and CD105
Fig. 3
Fig. 3
CONSORT flow diagram
Fig. 4
Fig. 4
Primary endpoint analysis

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