Bone marrow stromal cells exhibit multiple traits of a stem cell population. They
can be greatly expanded in vitro and induced to differentiate into multiple mesenchymal
cell types. However, differentiation to non-mesenchymal fates has not been demonstrated.
Here, adult rat stromal cells were expanded as undifferentiated cells in culture for
more than 20 passages, indicating their proliferative capacity. A simple treatment
protocol induced the stromal cells to exhibit a neuronal phenotype, expressing neuron-specific
enolase, NeuN, neurofilament-M, and tau. With an optimal differentiation protocol,
almost 80% of the cells expressed NSE and NF-M. The refractile cell bodies extended
long processes terminating in typical growth cones and filopodia. The differentiating
cells expressed nestin, characteristic of neuronal precursor stem cells, at 5 hr,
but the trait was undetectable at 6 days. In contrast, expression of trkA, the nerve
growth factor receptor, persisted from 5 hr through 6 days. Clonal cell lines, established
from single cells, proliferated, yielding both undifferentiated and neuronal cells.
Human marrow stromal cells subjected to this protocol also differentiated 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.
Copyright 2000 Wiley-Liss, Inc.