GFP labelled ES cell derived neural precursor cells differentiate into Thy-1 positive neurons and glia after transplantation into the striatum of the adult rat striatum

Stefan ArnholdInstitute of Anatomy I, Department of Stereotactic and Functional Neurosurgery, and Institute of Neurophysiology, University of Cologne, Germany

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Doris LenartzInstitute of Anatomy I, Department of Stereotactic and Functional Neurosurgery, and Institute of Neurophysiology, University of Cologne, Germany

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Klaus KruttwigInstitute of Anatomy I, Department of Stereotactic and Functional Neurosurgery, and Institute of Neurophysiology, University of Cologne, Germany

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Franz-Josef KlinzInstitute of Anatomy I, Department of Stereotactic and Functional Neurosurgery, and Institute of Neurophysiology, University of Cologne, Germany

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Eugen KolossovInstitute of Anatomy I, Department of Stereotactic and Functional Neurosurgery, and Institute of Neurophysiology, University of Cologne, Germany

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Jürgen HeschelerInstitute of Anatomy I, Department of Stereotactic and Functional Neurosurgery, and Institute of Neurophysiology, University of Cologne, Germany

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Volker SturmInstitute of Anatomy I, Department of Stereotactic and Functional Neurosurgery, and Institute of Neurophysiology, University of Cologne, Germany

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Christian AndressenInstitute of Anatomy I, Department of Stereotactic and Functional Neurosurgery, and Institute of Neurophysiology, University of Cologne, Germany

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Klaus AddicksInstitute of Anatomy I, Department of Stereotactic and Functional Neurosurgery, and Institute of Neurophysiology, University of Cologne, Germany

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Object. The aim of this investigation was to assess new information concerning the capacity of transplanted embryonic stem cell (ESC)-derived neuronal cells to migrate into host brain and to evaluate these cells as a possible source for cell replacement therapy in neurodegenerative disorders such as Parkinson's disease (PD).

Methods. The authors investigated the ability of ESC-derived neural precursor cells to migrate and differentiate in a host striatum by using a D3-derived ESC clone that was transfected stably with a chicken β-actin cytomegalovirus enhancer—driven green fluorescent protein (GFP)-labeled construct. This procedure allowed easy monitoring of all transplanted cells because of the green fluorescent labeling of donor cells. This approach also afforded easy estimation of cell integration and simultaneous observation of the entire transplanted cell population in relation to immunocytochemically identified neuronal and glial differentiation. After selection of nestin-positive neural precursor cells in a synthetic medium, they were implanted into the striatum of male adult Wistar rats. Their integration was analyzed on morphological studies performed 3 days to 4 weeks posttransplantation.

Conclusions. The investigators found that after transplantation, a subpopulation of GFP-labeled cells differentiated into various neural morphological types that were positive for the mouse-specific Thy-1 antigen, which is known be expressed on neurons, as well as being positive for the astroglial marker glial fibrillary acidic protein. Moreover, GFP-expressing cells that were negative for either of these markers remained close to the injection site, presumably representing other derivatives of the neural lineage. Together, these findings contribute to basic research regarding future transplantation strategies in neurodegenerative diseases such as PD.

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