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Stem cell transplantation in multiple sclerosis: current status and future prospects

Nature Reviews Neurology volume 6, pages 247–255 (2010)Cite this article

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Abstract

This article provides an overview of the current knowledge relating to the potential use of transplanted stem cells in the treatment of patients with multiple sclerosis (MS). Two types of stem cells, CNS-derived neural stem/precursor cells (NPCs) and bone marrow-derived mesenchymal stem cells (MSCs) are considered to provide reproducible and robust therapeutic effects when intravenously or intrathecally injected into both rodents and primates with experimental autoimmune encephalomyelitis. Furthermore, preliminary safety data concerning the use of intrathecally injected autologous MSCs in patients with progressive MS are available. We discuss how the data gathered to date challenge the narrow view that the therapeutic effects of NPCs and MSCs observed in the treatment of MS are accomplished solely by cell replacement. Both types of stem cell, when transplanted systemically, might instead influence disease outcome by releasing a plethora of factors that are immunomodulatory or neuroprotective, thereby directly or indirectly influencing the regenerative properties of intrinsic CNS stem/precursor cells.

Key Points

  • Therapies based on neural stem/precursor cells (NPCs) or mesenchymal stem cells (MSCs) might limit neuronal damage in patients with multiple sclerosis (MS) by directly or indirectly promoting neuroprotection via remyelination and immunomodulation

  • Intravenously or intrathecally delivered NPCs have immunomodulatory effects in both the CNS and the periphery; NPCs probably contribute directly to remyelination when delivered into areas of demyelination

  • Intravenously delivered MSCs have peripheral immunomodulatory effects and might indirectly influence remyelination

  • Exploratory trials using MSCs and NPCs to treat early secondary progressive MS that is refractory to conventional therapy should now be considered

  • The International Society for Stem Cell Research guidelines should be strictly followed, and patients should be discouraged from approaching non-regulated 'stem cell clinics'

  • All trials should be prospectively registered, and sharing of methodologies and data should be encouraged

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Figure 1: Therapeutic plasticity of stem cells.

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Acknowledgements

We wish to thank Doug Brown and Lee Dunster from the UK MS Society, John Richert and Patricia O'Looney from the National MS Society (USA), Tim Coetzee from Fast Forward, Mario Battaglia from the Italian MS Society and Emanuelle Plassart-Schiess from the French MS Society for calling the Stem Cells in Multiple Sclerosis (STEMS) Consensus Meeting and supporting its organization. G. Martino and R. J. M. Franklin contributed equally to this article.

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Authors and Affiliations

  1. Division of Neuroscience, Institute of Experimental Neurology–DIBIT 2, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy

    Gianvito Martino

  2. Department of Veterinary Medicine, MRC Center for Stem Cell Biology and Regenerative Medicine, University of Cambridge, Madingley Road, CB3 0ES, Cambridge, UK

    Robin J. M. Franklin

  3. INSERM U975, Université Pierre et Marie Curie-Paris, and AP-HP, Hôpital Pitié-Salpétrière, Fédération de Neurologie, F-75013, Paris, France

    Anne Baron Van Evercooren

  4. Johns Hopkins TM Center, Johns Hopkins Hospital, Broadway Research Building, Room 759, Baltimore, 21287-6965, MD, USA

    Douglas A. Kerr

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Martino, G., Franklin, R., Van Evercooren, A. et al. Stem cell transplantation in multiple sclerosis: current status and future prospects. Nat Rev Neurol 6, 247–255 (2010). https://doi.org/10.1038/nrneurol.2010.35

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