Bone
marrow stromal cells (MSC), which represent a population of multipotential
mesenchymal stem cells, have been reported to undergo rapid and robust
transformation into neuron-like phenotypes in vitro following treatment
with chemical induction medium including dimethyl sulfoxide
(abstract). In this study, we confirmed the ability of cultured
rat MSC to undergo in vitro osteogenesis, chondrogenesis, and adipogenesis
demonstrating differentiation of these cells to three mesenchymal cell
fates. We then evaluated the potential for in vitro neuronal differentiation
of these MSC, finding that changes in morphology upon addition of the
chemical induction medium were caused by rapid disruption of the actin
cytoskeleton. Retraction of the cytoplasm left behind long processes,
which, although strikingly resembling neurites, showed essentially no
motility and no further elaboration during time-lapse studies. Similar
neurite-like processes were induced by treating MSC with DMSO only,
or with actin filament-depolymerizing agents. Although process formation
was accompanied by rapid expression of some neuronal and glial markers,
the absence of other essential neuronal proteins pointed towards aberrantly
induced gene expression rather than towards a sequence of gene expression
as is required for neurogenesis. Moreover, rat dermal fibroblasts responded
to neuronal induction by forming similar processes and expressing similar
markers. These studies do not rule out the possibility that MSC can
differentiate into neurons, however, we do want to caution that in vitro
differentiation protocols may have unexpected, misleading effects. A
dissection of molecular signaling and commitment events may be necessary
to verify the ability of MSC transdifferentiation to neuronal lineages
(PDF).
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