New 3D Scaffolds Support Outgrowth and Survival of Transplanted Neurons in Vivo

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Culturing stem cells on substrates that are fabricated in three dimensions provides important advantages to their therapeutic potential. 3D scaffolds have thus emerged as powerful substrate systems for regenerative medicine applications. Significant advances in the technologies used to generate these systems have emerged, and some have even reached commercial status.

A new just-published study further expands the potential of 3D scaffolds in the treatment of CNS disorders.

Dr. Prabhas Moghe, Professor at the Department of Chemical and Biochemical Engineering at Rutgers University, and colleagues have developed a 3D micro-scaffold platform that promotes reprogramming of stem cells into neurons, and supports growth of neuronal connections capable of transmitting electrical signals.

Titled Generation and transplantation of reprogrammed human neurons in the brain using 3D microtopographic scaffolds, the study was published this week in the journal Nature.

The scaffolds are based on electrospun nanofibers – a technology that involves spinning long, thin fibers of various synthetic or natural materials into custom-aligned shapes.

The authors used aelectrospinning to generate fibrous substrates, while spin coating was used to create 2D polymer film controls from tyrosine-derived polycarbonate pDTEc.

The assumption was that such 3D microstructures would support neuronal networks that exhibit improved levels of retention and engraftment following transplantation into the brain.

Through a combination of scaffold geometry and media supplementation, the authors demonstrated suppression of proliferation of undifferentiated iPSCs.

After demonstrating successful engrafment of induced neuronal cells into the CNS in an ex vivo organotypic brain slice model, the authors followed this with an in vivo demonstration of scaffold functionality.

Screen Shot 2016-03-20 at 12.39.41 PM
GFP-expressing surviving iNs 3 weeks post transplantation in mouse striatum for dissociated induced neurons (b) and with induced neuron-seeded microscaffolds (c–e).

Transplantation of induced neuronal cells in 3D scaffolds into the mouse striatum showed that the percentage of viable cells after 3 weeks was an order-of-magnitude larger than that obtained with isolated single cells.

 

Screen Shot 2016-03-20 at 12.41.50 PM

The fiber material, the thickness of the fibers, their porosity and the scaffold geometry were identified as important factors that together play a critical role in the functionality of these scaffolds compared to standard 2D fibrous substrates.

You can see the open access paper here.

More questions about electrospinning? Need a custom scaffold system? Contact us here.

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