02:40am Monday 11 December 2017

Understanding how connections rewire after spinal cord injury

By Beth Miller
Restoring function after spinal cord injury, which damages the connections that carry messages from the brain to the body and back, depends on forming new connections between the surviving nerve cells. While there are some delicate surgical techniques that reconnect the nerves, researchers are also looking at ways to restore the connections themselves at a cellular level.

Mouse stem cells differentiated into spinal V2a interneuron enriched cultures (red = neuronal cells, blue = cell nuclei, green = V2a interneurons) to study their role in rewiring.

With a five-year, nearly $1.7 million grant from the National Institutes of Health, Shelly Sakiyama-Elbert, PhD, professor of biomedical engineering in the School of Engineering & Applied Science at Washington University in St. Louis, is using novel methods to take a closer look at how these nerve cells grow and make new connections to reroute signals between the brain and the body that could restore function and movement in people with these debilitating injuries.

Sakiyama-Elbert, also associate chair of the Department of Biomedical Engineering, is widely known for her groundbreaking work in tissue engineering techniques. Her research expertly blends biology, chemistry and biomedical engineering to focus on developing biomaterials for drug delivery and cell transplantation to treat peripheral nerve and spinal cord injury.

In the new research, funded by the National Institute of Neurological Disorders and Stroke, she and those who work in her lab want to understand how these nerve cells, or neurons, form connections and rewire after a spinal cord injury, looking closely at which particular cells, or interneurons, are forming these new connections.

“There have been a lot of studies where researchers have shown recovery in partial spinal cord injury models, but no one understands at a cellular level which cells are responsible for rewiring or forming the new connections,” Sakiyama-Elbert said. “If we want to make regeneration more efficient and potentially translatable to humans where it is more challenging, we need to understand what’s actually going on at a cellular level.

“Once we determine which cells are making connections, we can determine how to transplant more of those cells or try to stimulate tissue-specific stem cells to make those types of neurons and form these types of connections,” Sakiyama-Elbert said.

While much is known about motor neurons, less is known about these interneurons in culture or how to direct their connection with other neurons. Sakiyama-Elbert is developing new tools that will allow her to isolate very pure groups of different types of interneurons and then study what encourages them to grow and form new connections.

Using a new technology enabled by the Genome Engineering Center at the School of Medicine, Sakiyama-Elbert will select the interneurons she wants from cell samples and eliminate the other cells. This cell genome technology shortens this work to about a month from about six months using prior technologies, which will speed up the process significantly, Sakiyama-Elbert said.

In addition, she will use microdevices to help understand interactions between different populations of neurons or different populations of cells. With the microdevices, the researchers can control what kinds of interactions occur between cells.

“This research builds on our expertise of having previously transplanted scaffolds and cells into the spinal cord,” she said. “We also have expertise in drug delivery, so we can use that to help promote the survival of the cells and stimulate their growth and the formation of new connections.”

Sakiyama-Elbert, also member of the Center of Regenerative Medicine and the Hope Center for Neurological Disorders, is collaborating with Dennis Barbour, MD, PhD, associate professor of biomedical engineering, and James Huettner, PhD, professor of cell biology and physiology at the School of Medicine. Huettner, who specializes in differentiating pluripotent cells into neurons, will assess whether the cells Sakiyama-Elbert generates are similar to primary neurons taken from tissue, and Barbour will help with determining connectivity at a network or tissue level, Sakiyama-Elbert said.

About the School of Engineering & Applied Science

The School of Engineering & Applied Science focuses intellectual efforts through a new convergence paradigm and builds on strengths, particularly as applied to medicine and health, energy and environment, entrepreneurship and security.

With 91 tenured/tenure-track and 40 additional full-time faculty, 1,300 undergraduate students, more than 900 graduate students and more than 23,000 alumni, we are working to leverage our partnerships with academic and industry partners — across disciplines and across the world — to contribute to solving the greatest global challenges of the 21st century.


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