Reports have suggested that adult mouse bone marrow cells (BMCs) are capable of transdifferentiating into cells with neural characteristics in the central nervous system (CNS)(1, 2). Because side-population (SP) cells within whole bone marrow are hematopoietic stem cells that can reconstitute the BMC population and are capable of differentiating into other types of cells such as cardiac myocytes and endothelial cells (3–5), we surmised that they too would transdifferentiate into neural cells.

To test this, 8 C57Bl/6 (B6) mice were treated with a lethal dose of irradiation and transplanted with 2 103 SP cells derived from the Rosa26 mouse. The Rosa26 mouse carries the LacZ gene that is constitutively expressed in most cells including neural and SP cells and is an unambiguous marker for donor-derived cells (6). Ten to 12 weeks after transplantation, 80 to 95% of the recipient blood cells were LacZ positive. Four months after transplantation, the CNS of two of the recipient mice were inspected for cells derived from the Rosa26 donor with standard X-gal cytohistochemistry. In coronal sections (50 to 100 sections per brain representing more than 106 cells per brain) taken throughout the full extent of the brain, including the olfactory bulbs and cervical spinal cord, the only-galactosidase (-Gal)–positive cells detected were a few cells (5) that were associated with blood vessels. These-Gal–positive cells had a globular morphology and no processes that would suggest that they were neural