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From the Lab to Patients: a Systematic Review and Meta-Analysis of Mesenchymal Stem Cell Therapy for Stroke

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Abstract

There may be the potential to improve stroke recovery with mesenchymal stem cells (MSCs); however, questions about the efficacy and safety of this treatment remain. To address these issues and inform future studies, we performed a preclinical and clinical systematic review of MSC therapy for subacute and chronic ischemic stroke. MEDLINE, Embase, the Cochrane Register of Controlled Trials, and PubMed were searched. For the clinical review, interventional and observational studies of MSC therapy in ischemic stroke patients were included. For the preclinical review, interventional studies of MSC therapy using in vivo animal models of subacute or chronic stroke were included. Measures of safety and efficacy were assessed. Eleven clinical and 76 preclinical studies were included. Preclinically, MSC therapy was associated with significant benefits for multiple measures of motor and neurological function. Clinically, MSC therapy appeared to be safe, with no increase in adverse events reported (with the exception of self-limited fever immediately following injection). However, the efficacy of treatment was less apparent, with significant heterogeneity in both study design and effect size being observed. Additionally, in the only randomized phase II study to date, efficacy of MSC therapy was not observed. Preclinically, MSC therapy demonstrated considerable efficacy. Although MSC therapy demonstrated safety in the clinical setting, efficacy has yet to be determined. Future studies will need to address the discordance in the continuity of evidence as MSC therapy has been translated from “bench-to-bedside”.

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Acknowledgments

We would like to acknowledge Dr. Spencer Hey (Harvard Center for Bioethics) for his assistance with the AERO model and associated figure.

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Authors and Affiliations

  1. Department of Anesthesiology and Pain Medicine, The Ottawa Hospital Research Institute, Room B307, 1053 Carling Ave, Mail Stop 249, Ottawa, ON, K1Y 4E9, Canada

    Manoj M. Lalu & Ryan McGinn

  2. Clinical Epidemiology Program, Blueprint Translational Group, The Ottawa Hospital Research Institute, Ottawa, Canada

    Manoj M. Lalu, Joshua Montroy, Dar Dowlatshahi, Pascale Juneau, Neil Wesch & Dean A. Fergusson

  3. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada

    Manoj M. Lalu, Dale Corbett & Duncan J. Stewart

  4. Department of Medicine, Neurology, The Ottawa Hospital, Ottawa, Canada

    Dar Dowlatshahi

  5. Knowledge Synthesis Group, Ottawa Hospital Research Institute, Ottawa, Canada

    Brian Hutton & Dean A. Fergusson

  6. School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada

    Brian Hutton

  7. Faculty of Medicine, University of Ottawa, Ottawa, Canada

    Sarah Y. Zhang & Ryan McGinn

  8. Canadian Partnership for Stroke Recovery, Ottawa, Canada

    Dale Corbett

  9. Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada

    Duncan J. Stewart

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  1. Manoj M. Lalu
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Correspondence to Manoj M. Lalu.

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DS is an unpaid consultant and has an equity interest in Northern Therapeutics (Montréal, QC, Canada).

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Lalu, M.M., Montroy, J., Dowlatshahi, D. et al. From the Lab to Patients: a Systematic Review and Meta-Analysis of Mesenchymal Stem Cell Therapy for Stroke. Transl. Stroke Res. 11, 345–364 (2020). https://doi.org/10.1007/s12975-019-00736-5

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