Heparin Mimics and Fibroblast Growth Factor Fabricated Nanogold Composite in Promoting Neural Differentiation of Embryonic Stem Cells
24 Pages Posted: 9 Apr 2019
Date Written: April 8, 2019
The replacement therapy or transplantation using neural cells, which differentiated from stem cells, has emerged as a promising strategy for repairing damaged neural tissues and helping functional recovery in the treatment of neural system diseases. The challenge, however, is how to control embryonic stem cell fate so that neural differentiation can be efficiently directed to enrich a neuron cell population, and meanwhile to maintain their bioactivities. This is a key question and has a very significant impact in regenerative medicine. Here we proposed a new neural-differentiation inductive nanocomposite, containing gold nanoparticles (AuNPs), poly(2-methacrylamido glucopyranose-co-3-sulfopropyl acrylate) (PMS) , and fibroblast growth factor (FGF), for the high efficient directional neural-specific differentiation of embryonic stem cells (ESCs). In this AuNP-PMS/FGF composite, PMS, playing as the high-active mimic of heparin/heparan sulfate (HS), is covalently anchored to AuNPs and bound with FGFs on the surface of nanoparticles, forming a HS/FGF complex nanomimics to facilitate its binding to FGF receptor (FGFR) and promote high neural-inductive activity of ESCs. The stability, bioactivity and biocompatibility of the composite are investigated in this study. The results showed that the AuNP-PMS/FGF composite could maintain a long-term stability at room temperature for at least 8 days, and greatly promote the neural differentiation of ESCs. Compared with the other materials, the AuNP-PMS/FGF composite could significantly stimulate the expression of the specific neural differentiation markers (nestin and β3-tubulin), while obviously down-regulate the mRNA production of pluripotency marker Oct-4 in ESCs. Moreover, the promotion effect of the composite on neuronal maturation marker β3-tubulin expression achieved maximally at the low concentration of FGF (4 ng/mL), which suggested the high efficiency of AuNP-PMS/FGF composite in neural differentiation of ESCs. Meanwhile, both ESCs and L929 cells showed desirable growth during the incubation with AuNP-PMS/FGF composite. The AuNP-PMS/FGF system presents a new way to achieve HS/FGF complex nanomimics efficiently for the neural differentiation of ESCs.
Keywords: heparin mimics, fibroblast growth factor (FGF), gold nanoparticles (AuNPs), embryonic stem cells (ESCs), neural differentiation
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