Promoting the neural differentiation of embryonic stem cells by using thermosensitive nanocomposites

Abstract

Nerve cells differentiated from embryonic stem cells (ESCs) play an important role in the treatment of neurodegenerative diseases. Heparin has great potential for inducing ESCs to differentiate into nerve cells, but due to the shortcomings of heparin itself, its effect on inducing differentiation of ESCs is limited. In this study, the thermosensitive copolymer pNIPAAm-b-p(MAG-co-SPA) (pNMS) was synthesized with N-isopropylacrylamide (NIPAAm) as monomer and heparin mimic p(MAG-co-SPA) (pMS) as macromolecular chain transfer agent. Considering the biocompatibility of AuNPs, the nanocomposites were prepared, and their effects on inducing differentiation of ESCs were studied in detail. Compared to heparin, nanocomposites have a stronger effect on the differentiation of ESCs, especially AuNPs–pNMS, which can better promote the expression of β3-tubulin and stimulate the synthesis of proteins required for neuronal maturation. The results show that AuNPs–pNMS has a stronger ability to induce differentiation than AuNPs–pMS due to the presence of the pNIPAAm segment. The synergistic effect of pNIPAAm and pMS in AuNPs–pNMS greatly increases the efficiency of nanocomposite binding to FGFR, further enhancing the effect of the neural differentiation of ESCs. The effect of AuNPs–pNMS in promoting the differentiation of ESCs is also related to the relative molecular weight of pNMS. Under the premise of controlling the relative molecular weight of pMS to be 8900 Da, when the molecular weight of pNMS is 28 100 Da, AuNPs–pNMS has the strongest effect of promoting neural differentiation of ESCs. This thermosensitive nanocomposite provides a new strategy for promoting the neural differentiation of ESCs.