Designer Cells for Treating Arthritis Are Activated by Inflammation

Scientists have developed a new cell therapy for arthritis that becomes activated in the presence of inflammation. When implanted into cartilage, these genetically engineered cells mop up an inflammatory cytokine called interleukin-1 (IL-1) and ultimately resist bone erosion.

Over a million adults in the United States are living with rheumatoid arthritis, a chronic autoimmune disorder in which the body’s immune system mistakenly launches an unrelenting attack on the joints. Inflammation, pain, and swelling are hallmarks of the condition, which over time deform joints and significantly impact a patient’s quality of life.

Infusions of anti-inflammatory biologics drugs are currently administered to patients with rheumatoid arthritis. The problem, however, is repeated doses of such treatments can have serious side effects, prompting researchers to consider alternative approaches to addressing uncontrolled joint flare-ups in these patients.

To this end, researchers at the Washington University School of Medicine in St Louis have devised a method for reprogramming stem cells that, once implanted, sense the presence of inflammation and react by releasing a biologic treatment that lowers IL-1 levels in the joint. The therapeutic cells, housed within bioartificial implants, are reprogrammed using CRISPR-Cas9 gene editing. The implants would be placed under the skin or in a joint for months and react when inflammation levels begin to creep up. Administering the cells as an implant ensures the engineered cells stay in place and keep them alive for months.

The research team validated their implant in a mouse model of rheumatoid arthritis and, using advanced imaging techniques, demonstrated that the therapy prevented bone erosion in the animals while keeping inflammation at bay.

According to the researchers, the true value of using a CRISPR-Cas9 approach to engineer these cells is the potential to adapt the treatment to create a personalized medicine approach. In this case, bespoke cell therapies can be created for individual patients based on their responses to the treatment. Such a platform could also benefit the 300,000 children in the United States with a related inflammatory arthritis condition called juvenile arthritis.

Sources: Science Advances, Washington University School of Medicine in St. Louis.