Induction of neuronal markers in bone marrow cells: Differential effects of growth factors and patterns of intracellular expression

Bone marrow cells (BMC) can be induced to express neuronal phenotypic features in vitro, but the extent to which they can transdifferentiate to mature, functional neurons is uncertain. We examined the effects of different growth factors and combinations thereof on the expression of neuronal marker proteins in cultures of BMC enriched in marrow stromal cells. Patterns of neuronal marker expression varied depending on the growth factor or factors to which BMC cultures were exposed. Cultures treated for up to 5 weeks with epidermal growth factor, fibroblast growth factor-2, retinoic acid, and nerve growth factor displayed neuron-like cellular processes and expressed neuronal markers, including the neuronal nuclear antigen NeuN, microtubule-associated protein 2, tau, synaptophysin, α_1A and α_1B calcium channel subunits, NR2A glutamate receptor subunits, and γ-aminobutyric acid. However, the intracellular distribution of these markers was distinct from their usual distribution in mature neurons. We conclude that a variety of growth factors can drive BMC toward a neuronal phenotype or phenotypes, but that morphological neuronal features and the ectopic expression of neuronal proteins and neurotransmitters may not equate with the ability to execute normal neuronal functions.