Potential Effects of Human Bone Marrow Non- Mesenchymal Mononuclear Cells on Neuronal Differentiation

Bone marrow-derived stem cells have been widely studied as an alternative source of stem cells. Mesenchymal stem cells (MSCs) were mostly investigated and studies showed MSCs can promote neurogenesis. Little is known about the non-mesenchymal mononuclear cell fraction, which contains both hematopoietic and nonhematopoietic cells, including monocytes and endothelial progenitor cells. This study focused on unfractionated bone marrow mononuclear cells (BMMCs), which remained 72 h after MSCs were adhered to the culture plates. We showed that BMMC-conditioned medium promoted morphological changes of human SH-SY5Y neuroblastoma cells from an epithelial-like phenotype towards a neuron-like phenotype as indicated by an increase in neurite outgrowth, like those observed in retinoic acid (RA)-treated cells. The result could be explained by the effects of trophic factors released from BMMCs, as shown in the RT-PCR results that BMMCs expressed nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF). Similar results on the cell proliferation rate were also observed between RA-treated cells and cells cultured in BMMC-conditioned medium, suggesting that cells creased proliferating and differentiated into a neuronal phenotype. Using real-time RT-PCR, a significantly increased expression of tyrosine hydroxylase (TH) mRNA in SHSY5Y cells indicated that BMMC-conditioned medium induced catecholaminergic identities in differentiated SH-SY5Y cells.