Gene-edited stem cells raise hopes for arthritis vaccine

Scientists have successfully edited mice stem cells to combat arthritis-related inflammation, in research that could one day lead to a human vaccine to treat the chronic condition.

The edited stem cells are part of an emerging group known as SMART cells (stem cells modified for autonomous regenerative therapy) and are designed to develop into cartilage cells that have the ability to produce a type of anti-inflammatory drug known as a biologic.

This means that – at least in theory – they would not only replace lost cartilage but also continually protect joints and the surrounding tissue from the damage normally associated with chronic inflammation.

As a result, they could offer a dramatic improvement over conventional arthritis treatments, which target a molecule in the immune system known as TNF-alpha (tumour necrosis factor-alpha) responsible for producing inflammation. These drugs can be very effective at combating arthritis but as they impact on the entire immune system, can also produce some unwanted and often extremely unpleasant side-effects.

Study lead author Dr Farshid Guilak explains the research to Jim Dryden of Washington University BioMed Radio

The research, which has been published today in the journal Stem Cell Reports, was conducted by a network of US scientists from Washington University School of Medicine, Shriners Hospitals for Children, Duke University and Cytex Therapeutics.

The scientists hope to develop the research into a sophisticated vaccine that would allow highly targeted treatment of arthritis.

“Our goal is to package the rewired stem cells as a vaccine for arthritis, which would deliver an anti-inflammatory drug to an arthritic joint but only when it is needed,” said study lead author Dr Farshid Guilak, a professor of orthopedic surgery at Washington University School of Medicine.

“We want to use our gene-editing technology as a way to deliver targeted therapy in response to localized inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body.

“If this strategy proves to be successful, the engineered cells only would block inflammation when inflammatory signals are released, such as during an arthritic flare in that joint.”

A conceptual depiction of the edited stem cell, which was modified using CRISPR technology. Image courtesy of Ella Marushchenko

The SMART cells were developed by growing mice stem cells in a test tube and then editing them using CRISPR gene editing technology to change the way the stem cells responded to inflammation. They were then able to grow the modified stem cells in cartilage tissue-producing cells, which they found were protected from inflammation that would normally impact on non-edited cartilage tissue.

Having achieved this vital first stage, the researchers plan to attempt to first replicate the achievement in animals, before moving on to research in humans with a goal of producing a vaccine or other therapy that can be used on patients.

They also believe the approach could be used for cell types, and therefore different medical conditions.

“We believe this strategy also may work for other systems that depend on a feedback loop. In diabetes, for example, it’s possible we could make stem cells that would sense glucose and turn on insulin in response,” explained Guilak.

“We are using pluripotent stem cells, so we can make them into any cell type, and with CRISPR, we can remove or insert genes that have the potential to treat many types of disorders.”

DARPA plans to test whether electrically stimulating the brain can speed up learning

The US Defence agency, DARPA, is investing in a series of projects aimed at determining whether applying electrical stimulation to nerves can speed up the time it takes for linguists, intelligence analysts and cryptographers to learn the skills necessary for their roles.

To achieve this goal, DARPA is funding eight efforts at seven different institutions, as part of its Targeted Neuroplasticity Training (TNT) program.

“The Defense Department operates in a complex, interconnected world in which human skills such as communication and analysis are vital, and the Department has long pushed the frontiers of training to maximize those skills,” said Doug Weber, the TNT Program Manager.

“DARPA’s goal with TNT is to further enhance the most effective existing training methods so the men and women of our Armed Forces can operate at their full potential.”

Image courtesy of DARPA

The eight projects DARPA will be funding all focus, at least initially, on the fundamental science of brain plasticity and aim to conclude with human trials in healthy volunteers.

In one of two efforts DARPA is funding at the University of Florida, a team led by Dr. Kevin Otto will attempt to identify which neural pathways in the brain are activated by sending electrical impulses via the vagus nerve.

Lead researcher on that particular project and associate professor in the J. Crayton Pruitt Family Department of Biomedical Engineering, Kevin J. Otto, said: “Currently, they could spend 50 years of their careers, 80 hours a week, just doing training and still wouldn’t be qualified to do every single thing.

“So they’re always interested in increasing mechanisms of learning and memory.”

Image courtesy of University of Florida

The other project being funded at the University of Florida will see a team led by Karim Oweiss study the mechanisms by which cranial nerve stimulation can affect brain activity.

His lab will use advanced optical imaging that will produce extremely high-resolution images of brain dynamics to map the functional circuitry in areas of the brain responsible for executive function.

“We want to see if it’s possible to promote targeted changes in specific brain circuits to accelerate this process by stimulating the vagus nerve, which sends close to 80 percent of its output back to the brain,” Oweiss said.

“So if one knows that ‘brain area A’ talks to ‘brain area B’ when learning a new language, can we develop training protocols that promote the exchange between these two areas while leaving other areas unaltered? Then the person will learn at a faster rate and retain the skills for much longer.”

DARPA’s TNT project is intended to be a four-year program.

At the end of those four years, DARPA aims to demonstrate that TNT methods and technologies can yield at least a 30% improvement in learning rate and the performance of necessary skills over traditional training regimens.

Details of all eight TNT projects are available here.