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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

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: Partici...

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Autores principales: Amanat, Man, Majmaa, Anahita, Zarrabi, Morteza, Nouri, Masoumeh, Akbari, Masood Ghahvechi, Moaiedi, Ali Reza, Ghaemi, Omid, Zamani, Fatemeh, Najafi, Sharif, Badv, Reza Shervin, Vosough, Massoud, Hamidieh, Amir Ali, Salehi, Mona, Montazerlotfelahi, Hadi, Tavasoli, Ali Reza, Heidari, Morteza, Mohebi, Hossein, Fatemi, Ali, Garakani, Amir, Ashrafi, Mahmoud Reza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343813/
https://www.ncbi.nlm.nih.gov/pubmed/34362453
http://dx.doi.org/10.1186/s13287-021-02513-4
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author Amanat, Man
Majmaa, Anahita
Zarrabi, Morteza
Nouri, Masoumeh
Akbari, Masood Ghahvechi
Moaiedi, Ali Reza
Ghaemi, Omid
Zamani, Fatemeh
Najafi, Sharif
Badv, Reza Shervin
Vosough, Massoud
Hamidieh, Amir Ali
Salehi, Mona
Montazerlotfelahi, Hadi
Tavasoli, Ali Reza
Heidari, Morteza
Mohebi, Hossein
Fatemi, Ali
Garakani, Amir
Ashrafi, Mahmoud Reza
author_facet Amanat, Man
Majmaa, Anahita
Zarrabi, Morteza
Nouri, Masoumeh
Akbari, Masood Ghahvechi
Moaiedi, Ali Reza
Ghaemi, Omid
Zamani, Fatemeh
Najafi, Sharif
Badv, Reza Shervin
Vosough, Massoud
Hamidieh, Amir Ali
Salehi, Mona
Montazerlotfelahi, Hadi
Tavasoli, Ali Reza
Heidari, Morteza
Mohebi, Hossein
Fatemi, Ali
Garakani, Amir
Ashrafi, Mahmoud Reza
author_sort Amanat, Man
collection PubMed
description 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 × 10(7)) 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). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02513-4.
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spelling pubmed-83438132021-08-09 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 Amanat, Man Majmaa, Anahita Zarrabi, Morteza Nouri, Masoumeh Akbari, Masood Ghahvechi Moaiedi, Ali Reza Ghaemi, Omid Zamani, Fatemeh Najafi, Sharif Badv, Reza Shervin Vosough, Massoud Hamidieh, Amir Ali Salehi, Mona Montazerlotfelahi, Hadi Tavasoli, Ali Reza Heidari, Morteza Mohebi, Hossein Fatemi, Ali Garakani, Amir Ashrafi, Mahmoud Reza Stem Cell Res Ther Research 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 × 10(7)) 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). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02513-4. BioMed Central 2021-08-06 /pmc/articles/PMC8343813/ /pubmed/34362453 http://dx.doi.org/10.1186/s13287-021-02513-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Amanat, Man
Majmaa, Anahita
Zarrabi, Morteza
Nouri, Masoumeh
Akbari, Masood Ghahvechi
Moaiedi, Ali Reza
Ghaemi, Omid
Zamani, Fatemeh
Najafi, Sharif
Badv, Reza Shervin
Vosough, Massoud
Hamidieh, Amir Ali
Salehi, Mona
Montazerlotfelahi, Hadi
Tavasoli, Ali Reza
Heidari, Morteza
Mohebi, Hossein
Fatemi, Ali
Garakani, Amir
Ashrafi, Mahmoud Reza
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343813/
https://www.ncbi.nlm.nih.gov/pubmed/34362453
http://dx.doi.org/10.1186/s13287-021-02513-4
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