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.
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.”
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.”