October 11, 2021
Farshid Guilak, PhD, Mildred B. Simon Professor of Orthopaedic Surgery, is senior investigator of a Washington University School of Medicine team of researchers who have genetically engineered cells that when implanted in mice, deliver a biologic drug in response to inflammation. This could be significant in the approaches to treat patients with rheumatoid arthritis and the findings were published online in the Science Advances journal.
The goal of the researchers is to develop therapies for people with rheumatoid arthritis with minimal side effects. This treatment approach also aims to prevent damage to bones, known as bone erosion, which can be a side effect of anti-inflammatory drugs often used to treat the estimated 1.3 million adults in the United States with the debilitating condition.
“Doctors often treat patients who have rheumatoid arthritis with injections or infusions of anti-inflammatory biologic drugs, but those drugs can cause significant side effects when delivered long enough and at high enough doses to have beneficial effects,” explained Guilak. “We used CRISPR technology to reprogram the genes in stem cells. Then we created a small cartilage implant by seeding the cells on woven scaffolds, and we placed them under the skin of mice. The approach allows those cells to remain in the body for a long time and secrete a drug whenever there is a flare of inflammation.”
In this new study, Guilak, a co-director of the Washington University Center of Regenerative Medicine, and his team members combined previous strategies to expand on rheumatoid arthritis treatment. The research team used CRISPR-Cas9 genome editing technology to make cells that secrete a biologic drug in response to inflammation. They had previously developed scaffolding that they coat with stem cells and implant in joints to form cartilage. Guilak’s lab also built SMART cells (Stem cells Modified for Autonomous Regenerative Therapy) to alter genes in those cells to respond to inflammation by secreting drugs.
The researchers are continuing their experimentation with CRISPR-Cas9 and stem cell technology, and even exploring engineered cells that could manufacture more than one drug in response to different inflammation triggers.
For more information, visit the WashU School of Medicine Newsroom, or Washington University Orthopaedic Research.