Neuronal morphological change of size-sieved stem cells induced by neurotrophic stimuli

Size-sieved stem cells (SSCs) derived from human bone marrow have the ability to differentiate into bone, fat and cartilage. SSCs can differentiate into active neural cells after exposure to antioxidant agents. The aim of the present study is to understand if SSCs can be stimulated to differentiate into neurons in response to neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), pituitary adenylate cyclase-activating polypeptide (PACAP) and dibutyryl cAMP (dbcAMP). SSCs in a serum-free medium transform from a fibroblastic-like form to a multipolar morphology. Treatment of SSCs with GDNF, PACAP, and dbcAMP increased the production of neurofilament light protein (NF-L) and a cytoskeleton protein-alpha-tubulin. Examination of a vesicle protein-synapsin-1 or a neuronal progenitor marker-internexin in SSCs indicated that treatment with GDNF, PACAP, and dbcAMP further elongated cell processes and increased process branching. The findings indicate that neurotrophic signaling and cAMP-dependent signaling might promote the neuronal differentiation of SSCs.