Transplanted mesenchymal stem cells migrate toward brain lesions and differentiate into neurons, glial cells, and neural stem cells in diseased or injured animal models. The migratory routes and differentiation patterns of mesenchymal stem cells in normal rats are, however, unknown. Here, labelled human mesenchymal stem cells (or saline) were transplanted into the striatum of adult rats to observe their migration and differentiation.METHODS:Labelled human mesenchymal stem cells were transplanted into the right striatum of adults rats (n = 24). Brain sections were examined for migratory routes of labelled human mesenchymal stem cells by immunohistochemistry method, fluorescence microscope and laser scanning confocal microscopy observation, and Prussian blue staining. Moreover, the differentiation of human mesenchymal stem cells was detected by double immunohistochemistry.RESULTS:After 3 days, most human mesenchymal stem cells resided around the injection sites. Human mesenchymal stem cells were found in or around the corpus callosum and the subependymal layer after 7 days. A great number of human mesenchymal stem cells were detected throughout the brain on both ipsilateral and contralateral sides after 14 days. A high concentration of donor cells persisted in the corpus callosum, the external capsule and the subventricular zone. In addition, the incorporated human mesenchymal stem cells were neuronal nuclei- and glial fibrillary acidic protein-positive.CONCLUSION:Human mesenchymal stem cells migrate throughout the brain mainly along with the axis of corpus callosum external capsule and the subependymal layer, and differentiate into neurons and astrocytes rather than neural stem cells.