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Published 26 November 2001. doi:10.1083/jcb.200105103
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© The Rockefeller University Press, 0021-9525/2001/11/733 $5.00
The Journal of Cell Biology, Volume 155, Number 5, November 26, 2001 733-738

Report

Neogenesis of cerebellar Purkinje neurons from gene-marked bone marrow cells in vivo



Josef Priller1, Derek A. Persons2, Francisco F. Klett1, Gerd Kempermann3, Georg W. Kreutzberg4 and Ulrich Dirnagl1

1 Department of Neurology, Charité, Humboldt-University, 10117 Berlin, Germany
2 Department of Hematology and Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105
3 Max Delbrück Center for Molecular Medicine, 13125 Berlin-Buch, Germany
4 Max-Planck Institute of Neurobiology, 82152 Martinsried, 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: josef.priller{at}charite.de

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.

Key Words: bone marrow transplantation; gene transfer; green fluorescent protein; nervous system; Purkinje cells


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