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

The versatility of stem cells has only recently been fully recognized. Ther e is evidence that upon adoptive bone marrow (BM) transplantation (BMT), do nor-derived cells can give rise to neuronal phenotypes in the brains of rec ipient mice. Yet only few cells with the characteristic shape of neurons we re detected 1-6 mo post-BMT using transgenic or newborn mutant mice. To eva luate the potential of BM to generate mature neurons in adult C57BL/6 mice, we transferred the enhanced green fluorescent protein (GFP) gene into BM c ells using a murine stem cell virus-based retroviral vector. Stable and hig h level long-term GFP expression was observed in mice transplanted with the transduced BM. Engraftment of GFP-expressing cells in the brain was monito red by intravital microscopy. in a long-term follow up of 15 mo post-BMT, f ully developed Purkinje neurons were found to express GFP in both cerebella r hemispheres and in all chimeric mice. GFP-positive Purkinje cells were al so detected in BM chimeras from transgenic mice that ubiquitously express G FP. Based on morphologic criteria and the expression of glutamic acid decar boxylase, the newly generated Purkinje cells were functional.