The versatility of stem cells has only recently been fully recognized. There is evidence that upon adoptive bone marrow (BM) transplantation (BMT), donor-derived cells can give rise to neuronal phenotypes in the brains of recipient mice. Yet only few cells with the characteristic shape of neurons were detected 1–6 mo post-BMT using transgenic or newborn mutant mice. To evaluate the potential of BM to generate mature neurons in adult C57BL/6 mice, we transferred the enhanced green fluorescent protein (GFP) gene into BM cells using a murine stem cell virus-based retroviral vector. Stable and high level long-term GFP expression was observed in mice transplanted with the transduced BM. Engraftment of GFP-expressing cells in the brain was monitored by intravital microscopy. In a long-term follow up of 15 mo post-BMT, fully developed Purkinje neurons were found to express GFP in both cerebellar hemispheres and in all chimeric mice. GFP-positive Purkinje cells were also detected in BM chimeras from transgenic mice that ubiquitously express GFP. Based on morphologic criteria and the expression of glutamic acid decarboxylase, the newly generated Purkinje cells were functional.
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26 November 2001
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November 26 2001
Neogenesis of cerebellar Purkinje neurons from gene-marked bone marrow cells in vivo
Josef Priller,
Josef Priller
1Department of Neurology, Charité, Humboldt-University, 10117 Berlin, Germany
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Derek A. Persons,
Derek A. Persons
2Department of Hematology and Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105
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Francisco F. Klett,
Francisco F. Klett
1Department of Neurology, Charité, Humboldt-University, 10117 Berlin, Germany
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Gerd Kempermann,
Gerd Kempermann
3Max Delbrück Center for Molecular Medicine, 13125 Berlin-Buch, Germany
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Georg W. Kreutzberg,
Georg W. Kreutzberg
4Max-Planck Institute of Neurobiology, 82152 Martinsried, Germany
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Ulrich Dirnagl
Ulrich Dirnagl
1Department of Neurology, Charité, Humboldt-University, 10117 Berlin, Germany
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Josef Priller
1Department of Neurology, Charité, Humboldt-University, 10117 Berlin, Germany
Derek A. Persons
2Department of Hematology and Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105
Francisco F. Klett
1Department of Neurology, Charité, Humboldt-University, 10117 Berlin, Germany
Gerd Kempermann
3Max Delbrück Center for Molecular Medicine, 13125 Berlin-Buch, Germany
Georg W. Kreutzberg
4Max-Planck Institute of Neurobiology, 82152 Martinsried, Germany
Ulrich Dirnagl
1Department of Neurology, Charité, Humboldt-University, 10117 Berlin, Germany
Address correspondence to Josef Priller, Department of Neurology, Charité, Humboldt-University, Schumannstrasse 20/21, D-10117 Berlin, Germany. Tel.: (49) 30-450-560140. Fax: (49) 30-450-560932. E-mail: [email protected]
*
Abbreviations used in this paper: BM, bone marrow; BMT, BM transplantation; CNS, central nervous system; GABA, γ-aminobutyric acid; GAD, glutamic acid decarboxylase; GFAP, glial fibrillary acidic protein; GFP, green fluorescent protein.
Received:
May 22 2001
Revision Received:
September 13 2001
Accepted:
September 18 2001
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2001
J Cell Biol (2001) 155 (5): 733–738.
Article history
Received:
May 22 2001
Revision Received:
September 13 2001
Accepted:
September 18 2001
Citation
Josef Priller, Derek A. Persons, Francisco F. Klett, Gerd Kempermann, Georg W. Kreutzberg, Ulrich Dirnagl; Neogenesis of cerebellar Purkinje neurons from gene-marked bone marrow cells in vivo . J Cell Biol 26 November 2001; 155 (5): 733–738. doi: https://doi.org/10.1083/jcb.200105103
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