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, H A; Fatemi, Ali; Garakani, Amir

doi:10.1186/s13287-021-02513-4

Cited by 24 publications

(17 citation statements)

References 64 publications

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“…Therefore, we divided them into two groups for data extraction. Amanat et al (2021) and Liu et al (2017) included only patients with spastic CP in their studies. All the studies’ sample sizes ranged from 36 to 105 and were published from 2012 to 2021.…”

Section: Resultsmentioning

confidence: 99%

Efficacy and safety of stem cell therapy in cerebral palsy: A systematic review and meta-analysis

Zhou

Zhang

et al. 2022

Front. Bioeng. Biotechnol.

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Aim: Although the efficacy and safety of stem cell therapy for cerebral palsy has been demonstrated in previous studies, the number of studies is limited and the treatment protocols of these studies lack consistency. Therefore, we included all relevant studies to date to explore factors that might influence the effectiveness of treatment based on the determination of safety and efficacy.Methods: The data source includes PubMed/Medline, Web of Science, EMBASE, Cochrane Library, from inception to 2 January 2022. Literature was screened according to the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the outcome indicators of each study were extracted for combined analysis.Results: 9 studies were included in the current analysis. The results of the pooled analysis showed that the improvements in both primary and secondary indicators except for Bayley Scales of Infant and Toddler Development were more skewed towards stem cell therapy than the control group. In the subgroup analysis, the results showed that stem cell therapy significantly increased Gross Motor Function Measure (GMFM) scores of 3, 6, and 12 months. Besides, improvements in GMFM scores were more skewed toward umbilical cord mesenchymal stem cells, low dose, and intrathecal injection. Importantly, there was no significant difference in the adverse events (RR = 1.13; 95% CI = [0.90, 1.42]) between the stem cell group and the control group.Conclusion: The results suggested that stem cell therapy for cerebral palsy was safe and effective. Although the subgroup analysis results presented guiding significance in the selection of clinical protocols for stem cell therapy, high-quality RCTs validations are still needed.

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Section: Resultsmentioning

confidence: 99%

Efficacy and safety of stem cell therapy in cerebral palsy: A systematic review and meta-analysis

Zhou

Zhang

et al. 2022

Front. Bioeng. Biotechnol.

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“…MSCs derived from human umbilical cord tissue provide important benefits for cell therapeutics due to their immunosuppressive and anti-inflammatory properties and their ability to differentiate into various types of cells. 10,21 All isolation and early expansion procedures were performed by collaborators at the Marcus Center for Cellular Cures and approved by the Duke University Institutional Review Board.…”

Section: Methodsmentioning

confidence: 99%

Functional imaging with dynamic quantitative oblique back-illumination microscopy

Costa

Wang

Filan³

et al. 2022

J. Biomed. Opt.

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Significance: Quantitative oblique back-illumination microscopy (qOBM) is a recently developed label-free imaging technique that enables 3D quantitative phase imaging of thick scattering samples with epi-illumination. Here, we propose dynamic qOBM to achieve functional imaging based on subcellular dynamics, potentially indicative of metabolic activity. We show the potential utility of this novel technique by imaging adherent mesenchymal stromal cells (MSCs) grown in bioreactors, which can help address important unmet needs in cell manufacturing for therapeutics.Aim: We aim to develop dynamic qOBM and demonstrate its potential for functional imaging based on cellular and subcellular dynamics.Approach: To obtain functional images with dynamic qOBM, a sample is imaged over a period of time and its temporal signals are analyzed. The dynamic signals display an exponential frequency response that can be analyzed with phasor analysis. Functional images of the dynamic signatures are obtained by mapping the frequency dynamic response to phasor space and colorcoding clustered signals.Results: Functional imaging with dynamic qOBM provides unique information related to subcellular activity. The functional qOBM images of MSCs not only improve conspicuity of cells in complex environments (e.g., porous micro-carriers) but also reveal two distinct cell populations with different dynamic behavior. Conclusions:In this work we present a label-free, fast, and scalable functional imaging approach to study and intuitively display cellular and subcellular dynamics. We further show the potential utility of this novel technique to help monitor adherent MSCs grown in bioreactors, which can help achieve quality-by-design of cell products, a significant unmet need in the field of cell therapeutics. This approach also has great potential for dynamic studies of other thick samples, such as organoids.

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“…The trial protocol was explained in Supplement 1 . The detailed description of methods was also published previously [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

“…The protocol of imaging was previously explained [ 17 ]. The magnetic resonance imaging (MRI) was performed on 1.5 T scanner (Philips Ingenia, Eindhoven, the Netherlands).…”

Section: Methodsmentioning

confidence: 99%

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The safety and efficacy of umbilical cord blood mononuclear cells in individuals with spastic cerebral palsy: a randomized double-blind sham-controlled clinical trial

et al. 2022

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Introduction The current multi-center, randomized, double-blind study was conducted among children with cerebral palsy (CP) to assess the safety and efficacy of umbilical cord blood mononuclear cell (UCB-MNC). We performed the diffusion tensor imaging to assess the changes in the white matter structure. Methods Males and females aged 4 to 14 years old with spastic CP were included. Eligible participants were allocated in 4:1 ratio to be in the experimental or control groups; respectively. Individuals who were assigned in UCB-MNC group were tested for human leukocyte antigen (HLA) and fully-matched individuals were treated with UCB-MNCs. A single dose (5 × 106 /kg) UCB-MNCs were administered via intrathecal route in experimental group. The changes in gross motor function measure (GMFM)-66 from baseline to one year after treatment were the primary endpoints. The mean changes in modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also evaluated and compared between groups. The mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR) were the secondary endpoints. Adverse events were safety endpoint. Results There were 72 included individuals (36 cases in each group). The mean GMFM-66 scores increased in experimental group; compared to baseline (+ 9.62; 95%CI: 6.75, 12.49) and control arm (β: 7.10; 95%CI: 2.08, 12.76; Cohen’s d: 0.62) and mean MAS reduced in individuals treated with UCB-MNCs compared to the baseline (-0.87; 95%CI: -1.2, -0.54) and control group (β: -0.58; 95%CI: -1.18, -0.11; Cohen’s d: 0.36). The mean PEDI scores and mean CP-QoL scores in two domains were higher in the experimental group compared to the control. The imaging data indicated that mean FA increased and MD decreased in participants of UCB-MNC group indicating improvements in white matter structure. Lower back pain, headaches, and irritability were the most common adverse events within 24 h of treatment that were related to lumbar puncture. No side effects were observed during follow-up. Conclusions This trial showed that intrathecal injection of UCB-MNCs were safe and effective in children with CP. Trial Registration The study was registered with ClinicalTrials.gov (NCT03795974).

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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

Cited by 24 publications

References 64 publications

Efficacy and safety of stem cell therapy in cerebral palsy: A systematic review and meta-analysis

Efficacy and safety of stem cell therapy in cerebral palsy: A systematic review and meta-analysis

Functional imaging with dynamic quantitative oblique back-illumination microscopy

The safety and efficacy of umbilical cord blood mononuclear cells in individuals with spastic cerebral palsy: a randomized double-blind sham-controlled clinical trial

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