Directing neural differentiation of mesenchymal stem cells by carboxylated multiwalled carbon nanotubes

The use of carbon nanotubes (CNTs) to promote neural differentiation is well known. However, most studies have focused on the effect of CNT-derived composites or CNT-based nanopattern substrates on differentiation. Whether or not the intrinsic properties of CNTs themselves can affect neural differentiation and the differentiation mechanism have not been fully investigated. We demonstrated that carboxylated multiwalled carbon nanotubes (MWCNTs) can induce and maintain neural differentiation of human bone marrow mesenchymal stem cells (hBMMSCs) without any exogenous differentiating factors, as evidenced by the protein expression. The low cytotoxicity of carboxylated MWCNTs was also shown by a proliferation assay. Quantitative real-time polymerase chain reaction (Q-PCR) data revealed that neural-associated genes, including growth and transcription factors, were promoted while bone-associated genes were inhibited when the cells were cultured on carboxylated MWCNTs. These up-regulated neural growth factors can also adsorb onto carboxylated MWCNTs. The data suggest that carboxylated MWCNTs play dual roles: promoting hBMMSC neural differentiation, including up-regulating the neural growth factors; and trapping these neural growth factors to create a suitable environment for long-term neural differentiation. Carboxylated MWCNT substrates may provide a method of post-transplantational spontaneous neural differentiation with low cytotoxicity for neuron injury repair.