Proliferation and differentiation of neural stem cells on lysine–alanine sequential polymer substrates

The purpose of this study was to explore the phenotypic potential of embryonic rat cerebral cortical stem cells by inducing differentiation on lysine–alanine sequential (LAS) polymer substrates at neurosphere level. LAS polymer is a heterologous polymer of lysine and alanine and has been demonstrated to enhance axon growth of neurons in a serum-free medium in vitro. It was found that very few cells migrated outside of the neurospheres but extremely long processes extended from differentiated cells could form a network between remote neurospheres when cells were cultured on LAS substrates at a low density of 120 neurospheres/cm2 in the serum-free medium. On the contrary, when the neurosphere density was increased to 360 neurospheres/cm2, many neurosphere-forming cells migrated out from their original aggregate and exhibited short processes morphology. Furthermore, when serum was added to the culture system, the neurosphere-forming cells could be induced into an extensive cellular substratum of protoplasmic cells upon which process-bearing cells spread. Clearly, neurospheres could exhibit different behaviors on LAS substrates according to the complex environmental conditions. Here, we proposed that neurospheres would change their social communication and adopt different strategies to communicate with other neurospheres when they detected each other's presence. Therefore, the mediation of cell behavior on LAS substrates by communication between neurospheres should be taken into account.