Safety and Immunological Effects of Mesenchymal Stem Cell Transplantation in Patients With Multiple Sclerosis and Amyotrophic Lateral Sclerosis
By D. Karussis, C. Karageorgiou, A. Vaknin-Dembinsky, B. Gowda-Kurkalli, J. Gomori, I. Kassis, J. Bulte, P. Petrou, T. Ben-Hur, O. Abramsky and 1 more. Archives of Neurology, 2010
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Objective To evaluate the feasibility, safety, and immunological effects of intrathecal and intravenous administration of autologous mesenchymal stem cells (MSCs) (also called mesenchymal stromal cells) in patients with multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Design A phase 1/2 open-safety clinical trial. Patients Fifteen patients with MS (mean [SD] Expanded Disability Status Scale [EDSS] score, 6.7 [1.0]) and 19 with ALS (mean [SD] Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS] score, 20.8 [8.0]) were enrolled. Intervention After culture, a mean (SD) of 63.2 × 106 (2.5 × 106) MSCs was injected intrathecally (n=34) and intravenously (n=14). In 9 cases, MSCs were magnetically labeled with the superparamagnetic iron oxide ferumoxides (Feridex). Main Outcome Measures The main outcome measure was the recording of side effects. Follow-up (≤25 months) included adverse events evaluation, neurological disability assessment by means of the EDSS, magnetic resonance imaging to exclude unexpected pathologies and track the labeled stem cells, and immunological tests to assess the short-term immunomodulatory effects of MSC transplantation. Results Twenty-one patients had injection-related adverse effects consisting of transient fever, and 15 reported headache. No major adverse effects were reported during follow-up. The mean ALSFRS score remained stable during the first 6 months of observation, whereas the mean (SD) EDSS score improved from 6.7 (1.0) to 5.9 (1.6). Magnetic resonance imaging visualized the MSCs in the occipital horns of the ventricles, indicating the possible migration of ferumoxides-labeled cells in the meninges, subarachnoid space, and spinal cord. Immunological analysis revealed an increase in the proportion of CD4+ CD25+ regulatory T cells, a decrease in the proliferative responses of lymphocytes, and the expression of CD40+, CD83+, CD86+, and HLA-DR on myeloid dendritic cells at 24 hours after MSC transplantation. Conclusion Transplantation of MSCs in patients with MS and ALS is a clinically feasible and relatively safe procedure and induces immediate immunomodulatory effects.
Subfields: Genetics, Neurology
View Paper: https://www.semanticscholar.org/paper/df59f881bc846ed0a0ab628d63d107250f5485e9
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Citations in the corpus
- Mesenchymal stem cells and immunomodulation: current status and future prospects (2016, background): “In pediatric patients with chronic GvHD following allogeneic stem cell transplantation, one of three patients showed slight improvement following allogeneic BM-MSC infusion.83 Allogeneic BM-MSCs have also been shown by other clinical trials to be beneficial in GvHD.84–88 Recently, Health Canada has ”
- Safety of Cell Therapy with Mesenchymal Stromal Cells (SafeCell): A Systematic Review and Meta-Analysis of Clinical Trials (2012, methodology): “[17,18,26,27,29,31,33,35] Five studies explicitly reported and separated serious from non-serious adverse events; [13,14,20,24,46] two of these referenced a standardized approach to detailing adverse events developed by other organizations.”
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- Emerging trends and new developments in regenerative medicine: a scientometric update (2000 – 2014) (2014, background): “2010 Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis ARCH NEUROL-CHICAGO [78] Emerging trends and new developments in regenerative medicine”