Year-end Sale % OFF 
Abstract
Direct-lineage conversion of the somatic cell by reprogramming, in which mature cells were fully converted into a variety of other cell types bypassing an intermediate pluripotent state, is a promising regenerative medicine approach. Due to the risk of tumorigenesis by viral methods, a non-viral carrier for the delivery of reprogramming factors is very desirable. This study utilized the mesoporous silica nanoparticles (MSNs) as a non-viral delivery system for transduction of the three key factors to achieve conversion of mouse fibroblasts (MFs) into functional dopaminergic neuron-like cells (denoted as fDA-neurons). At the same time, a neurogenesis inducer, ISX-9, was co-delivered with the MSNs to promote the direct conversion of neuron-like cells. Good transfection efficiency of plasmid@MSN allowed repeated dosing to maintain high exogenous gene expression analyzed by qPCR and the changes in neural function markers were monitored. To further validate the dopaminergic function and the electrophysiological properties of fDA-neurons, the results of ELISA assay showed the high levels of secreted-dopamine in the conditional medium and rich Na+/K+-channels were observed in the fDA-neurons on Day 22. The results demonstrated that MSN nanocarrier is effective in delivering the reprogramming factors for the conversion of functional dopaminergic neurons from adult somatic cells.
Highlights
For future therapeutic direct conversion of cells, a limitation that needs to be overcome is that the introduction of viruses into human subjects is generally undesirable
To develop a stimulation-response non-viral nanoparticle for loading and delivering ISX-9, the pores of mesoporous silica nanoparticles (MSNs)-biotin were capped by avidin with the strong biotin-avidin interaction to give MSN-avi
The weight percentage of the biomolecules (-NH2-biotin-NHS and the avidin protein) modified on the mesoporous silica nanoparticles were 8.02% and 11.45%, respectively as determined by thermogravimetric analysis (TGA) a(Fbisgo.r2pct)io. nInbaadndditaito1n5,4th1ean-NdH1525-b7iocmtin−1a(nFdig–. i2odti,en)-.avidin modification on the MSNs was examined by the FTIR
Summary
Reprogramming Fibroblasts by Received: 8 September 2017 Accepted: 1 December 2017 Published: xx xx xxxx. This study utilized the mesoporous silica nanoparticles (MSNs) as a non-viral delivery system for transduction of the three key factors to achieve conversion of mouse fibroblasts (MFs) into functional dopaminergic neuron-like cells (denoted as fDA-neurons). We recently applied mesoporous silica nanoparticles (MSNs) to co-deliver Nurr[1] plasmid (pNurr1) and Rex[1] siRNA (siRex1) to iPSCs (Induced pluripotent stem cells) to achieve dopaminergic neuron differentiation Such differentiation process from iPSC could have the limitations of long-term differentiation schedule and lower efficient rat of dopaminergic-positive cells. We demonstrate a non-viral delivery system based on MSN for plasmid and drug co-delivery for direct conversion of fibroblast cells to neurons. The non-viral delivery system is tested for dual delivery of genes and hydrophobic drug into fibroblast to induce the direct conversion of MFs into functional dopaminergic neurons
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
