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Randomized Controlled Trial
. 2021 Aug 6;12(1):439.
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

Man Amanat  1 , Anahita Majmaa  2 , Morteza Zarrabi  3 , Masoumeh Nouri  3 , Masood Ghahvechi Akbari  2 , Ali Reza Moaiedi  4 , Omid Ghaemi  5 , Fatemeh Zamani  5 , Sharif Najafi  6 , Reza Shervin Badv  2 , Massoud Vosough  3 , Amir Ali Hamidieh  7 , Mona Salehi  8 , Hadi Montazerlotfelahi  9 , Ali Reza Tavasoli  2 , Morteza Heidari  2 , Hossein Mohebi  10 , Ali Fatemi  11   12 , Amir Garakani  13   14 , Mahmoud Reza Ashrafi  15
Affiliations
Randomized Controlled Trial

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 et al. Stem Cell Res Ther. .

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.

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Conflict of interest statement

The authors declare that they have no competing interests.

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
See this image and copyright information in PMC

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