Transplantation of human embryonic stem cell-derived neural precursor cells and enriched environment after cortical stroke in rats: cell survival and functional recovery

Authors

  • Anna U. Hicks,

    1. Department of Neurology, University of Kuopio, Kuopio, Finland
    2. Division of BioMedical Sciences, Faculty of Medicine, Memorial University, St John’s, NL, Canada
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    • *

      A.U.H. and R.S.L. contributed equally to this work.

  • Riikka S. Lappalainen,

    1. Regea, Institute for Regenerative Medicine, University of Tampere and Tampere University Hospital, Tampere, Finland
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    • *

      A.U.H. and R.S.L. contributed equally to this work.

  • Susanna Narkilahti,

    1. Regea, Institute for Regenerative Medicine, University of Tampere and Tampere University Hospital, Tampere, Finland
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  • Riitta Suuronen,

    1. Regea, Institute for Regenerative Medicine, University of Tampere and Tampere University Hospital, Tampere, Finland
    2. Department of Eye, Ear and Oral Diseases, Tampere University Hospital, Tampere, Finland
    3. Department of Biomedical Engineering, Tampere University of Technology, Tampere, Finland
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  • Dale Corbett,

    1. Division of BioMedical Sciences, Faculty of Medicine, Memorial University, St John’s, NL, Canada
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  • Juhani Sivenius,

    1. Department of Neurology, University of Kuopio, Kuopio, Finland
    2. Brain Research and Rehabilitation Center Neuron, Kuopio, Finland
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  • Outi Hovatta,

    1. Regea, Institute for Regenerative Medicine, University of Tampere and Tampere University Hospital, Tampere, Finland
    2. Karolinska Institutet, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital, Stockholm, Sweden
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  • Jukka Jolkkonen

    1. Department of Neurology, University of Kuopio, Kuopio, Finland
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Dr A. U. Hicks, 1Department of Neurology, as above.
E-mail: Anna.Rissanen@uku.fi

Abstract

Cortical stem cell transplantation may help replace lost brain cells after stroke and improve the functional outcome. In this study, we transplanted human embryonic stem cell (hESC)-derived neural precursor cells (hNPCs) or vehicle into the cortex of rats after permanent distal middle cerebral artery occlusion (dMCAO) or sham-operation, and followed functional recovery in the cylinder and staircase tests. The hNPCs were examined prior to transplantation, and they expressed neuroectodermal markers but not markers for undifferentiated hESCs or non-neural cells. The rats were housed in either enriched environment or standard cages to examine the effects of additive rehabilitative therapy. In the behavioral tests dMCAO groups showed significant impairments compared with sham group before transplantation. Vehicle groups remained significantly impaired in the cylinder test 1 and 2 months after vehicle injection, whereas hNPC transplanted groups did not differ from the sham group. Rehabilitation or hNPC transplantation had no effect on reaching ability measured in the staircase test, and no differences were found in the cortical infarct volumes. After 2 months we measured cell survival and differentiation in vivo using stereology and confocal microscopy. Housing had no effect on cell survival or differentiation. The majority of the transplanted hNPCs were positive for the neural precursor marker nestin. A portion of transplanted cells expressed neuronal markers 2 months after transplantation, whereas only a few cells co-localized with astroglial or oligodendrocyte markers. In conclusion, hESC-derived neural precursor transplants provided some improvement in sensorimotor function after dMCAO, but did not restore more complicated sensorimotor functions.

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