Researchers have used gene-editing technology and stem cells modified for autonomous regenerative therapy (SMART) to help fight arthritis. Arthritis and many other chronic conditions are associated with inflammation. The idea is to replace arthritic cartilage in the affected joints with stem-cell-produced cartilage and a biological anti-inflammatory agent.
New Research into Arthritis Therapy
Investigators at the Washington University School of Medicine and the Shriners Hospitals for Children in St. Louis have collaborated with researchers from Cytex Therapeutics and Duke University in Durham, NC. Initially, the team took the skin cells of mouse tails and created stem cells from these in the lab. Then the key gene that mediates the inflammatory response was removed from these cells with the help of CRISPR, a gene-editing tool. Instead, the scientists inserted a gene that produces a biological agent that fights inflammation. The findings were published in the journal Stem Cell Reports.
Gene-Editing Technology May Help Fight Arthritis
The ultimate goal of arthritis treatment is to develop a stem cell-based vaccine that would deliver anti-inflammatory agents on demand when needed. Essentially, this would be a smart cell that would respond to arthritic joints, explains Farshid Guilak, Ph.D., professor of orthopedic surgery and senior study author.
Current therapies for arthritis, such as Humira, Enbrel, and Remicade, rely on stopping the action of a molecule called TNF-alpha (tumor necrosis factor-alpha). TNF-alpha is an inflammation-producing agent. However, these pharmacotherapeutic agents have a systemic effect and do not specifically target the affected joints. The systemic action of these drugs is associated with a number of side effects including low immunity with a susceptibility to infections.
Targeted Therapy for Arthritic Joints
Since current therapies interfere with the immune process throughout the body, the goal is to develop targeted therapies that only act on arthritic joints. Gene-editing technology can help accomplish this. Engineered cells will respond to a signal of arthritic flares and release anti-inflammatory molecules to block the action of TNF-alpha.
The team used CRISPR technology to insert a TNF-alpha inhibitor in mouse stem cells. This type of gene modification allows scientists to orchestrate the inflammatory response, explains Jonathan Brunger, Ph.D., a postdoctoral fellow in the department of cellular and molecular pharmacology at UCSF. The team induced the gene-modified stem cells to grow cartilage and found that this cartilage was inflammation proof. The stem cells were tagged so that their response to inflammation could be observed.
This hijacking of the inflammatory pathway is a novel approach to produce a protective drug for arthritic joints. The idea is to develop a therapy with a feedback loop, i.e., stem cells that respond to signals. Pluripotent stem cells can mature into any type of cell. CRISPR technology allows scientists to insert and remove genes as needed to treat a variety of medical conditions. Ultimately, the researchers hope to create a smart tissue in the laboratory that closely simulates natural living tissue.