Graphene helps stem cells to differentiate

GrapheneHelpsStemCellsToDifferentiate
Stem cells can be turned into Schwann-like cells by growing them on printed, multi-layer graphene circuits and treating them with electricity

Original source: Materials Today

Researchers looking for ways to regenerate nerves can have a hard time obtaining the key tools of their trade.

Take Schwann cells, which form sheaths around axons – the tail-like parts of nerve cells that carry electrical impulses – and also promote regeneration of those axons and secrete substances that promote the health of nerve cells. In other words, they’re very useful to researchers hoping to regenerate nerve cells, especially peripheral nerve cells outside the brain and spinal cord. But Schwann cells are hard to come by in useful numbers.

So researchers have been taking readily-available and non-controversial mesenchymal stem cells (also known as bone marrow stromal stem cells, because they can form bone, cartilage and fat cells) and using a chemical process to turn them, or differentiate them, into Schwann cells. But it’s an arduous, step-by-step and expensive process.

Researchers at Iowa State University are now exploring what they hope will be a better way to transform mesenchymal stem cells into Schwann-like cells. They’ve developed a nanotechnology-based process that involves using inkjet printers to print multi-layer graphene circuits, and then lasers to treat and improve the surface structure and conductivity of those circuits.

It turns out that mesenchymal stem cells adhere and grow well on the treated circuit’s raised, rough and three-dimensional (3D) nanostructures. Add small doses of electricity – 100 millivolts for 10 minutes per day over 15 days – and the stem cells differentiate into Schwann-like cells.

The researchers’ findings are reported in a paper in Advanced Healthcare Materials, and are also featured on the front cover. Jonathan Claussen, an Iowa State assistant professor of mechanical engineering and an associate at the US Department of Energy’s Ames Laboratory, is lead author. Suprem Das, a postdoctoral research associate in mechanical engineering and an associate of the Ames Laboratory, and Metin Uz, a postdoctoral research associate in chemical and biological engineering, are first authors.

“This technology could lead to a better way to differentiate stem cells,” said Uz. “There is huge potential here.”

The electrical stimulation is very effective, differentiating 85% of the stem cells into Schwann-like cells, compared to 75% for the standard chemical process. The electrically-differentiated cells also produced 80 nanograms per milliliter of nerve growth factor compared to 55 nanograms per milliliter for the chemically-treated cells.

The researchers report that the results could lead to changes in how nerve injuries are treated inside the body. “These results help pave the way for in vivo peripheral nerve regeneration where the flexible graphene electrodes could conform to the injury site and provide intimate electrical stimulation for nerve cell regrowth,” the researchers wrote in a summary of their findings.

The paper reports several advantages to using electrical stimulation to differentiate stem cells into Schwann-like cells. These include: doing away with the arduous steps of chemical processing; reducing costs by eliminating the need for expensive nerve growth factors; potentially increasing control of stem cell differentiation with precise electrical stimulation; and creating a low maintenance, artificial framework for neural damage repairs.

A key to making it all work is the graphene inkjet printing process developed in Claussen’s research lab. This process takes advantage of graphene’s wonder-material properties – it’s a great conductor of electricity and heat, and is strong, stable and biocompatible – to produce low-cost, flexible and even wearable electronics.

But there is a problem: once the graphene electronic circuits are printed, they have to be treated to improve their electrical conductivity. That usually means exposing them to high temperatures or chemicals, and either could damage flexible printing surfaces including plastic films or paper.

Claussen and his research group solved the problem by replacing the high temperatures and chemicals with computer-controlled laser technology. This laser treatment removes ink binders and reduces graphene oxide to graphene – physically stitching together millions of tiny graphene flakes – improving the electrical conductivity more than a thousand times.

This collaboration between Claussen’s group of nanoengineers developing printed graphene technologies and Mallapragada’s group of chemical engineers working on nerve regeneration began with some informal conversations on campus. That led to experimental attempts to grow stem cells on printed graphene and then to electrical stimulation experiments.

“We knew this would be a really good platform for electrical stimulation,” Das said. “But we didn’t know it would differentiate these cells.”

But now that it has, the researchers say there are new possibilities to think about. The technology, for example, could one day be used to create dissolvable or absorbable nerve regeneration materials that could be surgically placed in a person’s body and wouldn’t require a second surgery to remove.