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Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome

Nature Neuroscience volume 8, pages 346353 (2005) | Download Citation

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Abstract

Several studies have reported functional improvement after transplantation of neural stem cells into injured spinal cord. We now provide evidence that grafting of adult neural stem cells into a rat thoracic spinal cord weight-drop injury improves motor recovery but also causes aberrant axonal sprouting associated with allodynia-like hypersensitivity of forepaws. Transduction of neural stem cells with neurogenin-2 before transplantation suppressed astrocytic differentiation of engrafted cells and prevented graft-induced sprouting and allodynia. Transduction with neurogenin-2 also improved the positive effects of engrafted stem cells, including increased amounts of myelin in the injured area, recovery of hindlimb locomotor function and hindlimb sensory responses, as determined by functional magnetic resonance imaging. These findings show that stem cell transplantation into injured spinal cord can cause severe side effects and call for caution in the consideration of clinical trials.

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Acknowledgements

We thank E. Lindqvist, K. Pernold and K. Lundströmer for outstanding technical assistance. This study was supported by grants from AMF, the Swedish Research Council, the Karolinska Institute, the Swedish Cancer Society, the Tobias Foundation, the Göran Gustafsson Foundation, the US Public Health Service, the European Union and the Foundation for Strategic Research. S.K. was supported by a Van Wagenen fellowship from the AANS.

Author information

Affiliations

  1. Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden.

    • Christoph P Hofstetter
    • , Johan A Lilja
    • , Petra Schweinhardt
    • , Christian Spenger
    •  & Lars Olson
  2. Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden.

    • Niklas A V Holmström
    •  & Jonas Frisén
  3. Division of Clinical Neurophysiology, Karolinska Institutet, 17177 Stockholm, Sweden.

    • Jinxia Hao
    •  & Zsuzsanna Wiesenfeld-Hallin
  4. Department of Human Anatomy, and Genetics, University of Oxford, OX1 1QX Oxford, UK.

    • Petra Schweinhardt
  5. Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.

    • Shekar N Kurpad

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The authors declare no competing financial interests.

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Correspondence to Christoph P Hofstetter.

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    Supplementary Fig. 1

    Immunohistochemical detection of Ngn2 two weeks following grafting.

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DOI

https://doi.org/10.1038/nn1405