Adult rat and human bone marrow stromal cells differentiate into neurons

cell population. They can be greatly expanded in vitro and induced to diffe rentiate into multiple mesenchymal cell types. However, differentiation to non-mesenchymal fates has not been demonstrated. Here, adult rat stromal ce lls were expanded as undifferentiated cells in culture for more than 20 pas sages, indicating their proliferative capacity. A simple treatment protocol induced the stromal cells to exhibit a neuronal phenotype, expressing neur on-specific enolase, NeuN, neurofilament-M, and tau. With an optimal differ entiation protocol, almost 80% of the cells expressed NSE and NF-M. The ref ractile cell bodies extended long processes terminating in typical growth c ones and filopodia. The differentiating cells expressed nestin, characteris tic of neuronal precursor stem cells, at 5 hr, but the trait was undetectab le at 6 days. In contrast, expression of trkA, the nerve growth factor rece ptor, persisted from 5 hr through 6 days. Clonal cell lines, established fr om single cells, proliferated, yielding both undifferentiated and neuronal ells. Human marrow stromal cells subjected to this protocol also differenti ated into neurons. Consequently, adult marrow stromal cells can be induced to overcome their mesenchymal commitment and may constitute an abundant and accessible cellular reservoir for the treatment of a variety of neurologic diseases. (C) 2000 Wiley-Liss, Inc.