In February, we reported on Dr. Farshid Guilak’s current Arthritis Foundation-funded trailblazing project, “Engineering New Biologic Therapies for Arthritis.”
Dr. Guilak’s work is published in the journal Stem Cell Reports. The paper, entitled “Genome engineering of stem cells for autonomously regulated, closed-loop delivery of biologic drugs,” describes the research team’s method of engineering (reprogramming) stem cells to become “smart stem cells” that will sense inflammation and deliver biologic drugs where they are most needed. The smart stem cells-biologic drug combination is then injected into an arthritic joint.
“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,” Dr. Guilak explained. “To do this, we needed to create a ‘smart’ cell.”
Once the inflamed cells are identified, the smart stem cells incorporate themselves, not only to repair damaged cartilage, but also to produce and deliver specific therapeutic drugs to stop the inflammation. The smart stem cells are programmed to be active only when and where inflammation is present.
He explained that this application is currently aimed at inflammatory diseases like rheumatoid arthritis (RA) and that the advantage of using smart stem cells is that they can be individually designed to deliver just the right amount of therapy, instead of a constant, long-term exposure to very strong anti-inflammatory drugs. Dr. Guilak said that the smart stem cells will stop the inflammation and repair damaged cells at the same time.
In mouse models, the team also found, that the cartilage repaired by the engineered smart stem cell is protected from inflammation. The team observed that the newly created cartilage cells change the inflammation pathway and produce a protective drug.
For his next steps with this technology, Dr. Guilak and his team will test the engineered smart cells in larger animals and then, if the results continue to be positive, move to clinical trials in humans. The team’s goal is to have the engineered cells or the newly grown synthetic cartilage from stem cells to respond to inflammation by releasing a biologic drug that would protect the synthetic cartilage cells and the natural cartilage cells in specific joints.
Dr. Guilak and his team feel that this research has tremendous applications that can be adapted for therapy for other inflammatory diseases, such as juvenile arthritis (JA) or psoriatic arthritis (PsA). “The inflammatory processes are different for these diseases than RA,” he explained. “So, we need to adjust the programming.”
According to Dr. Jonathan Brunger, research team member and first author of the paper, “The ability to build living tissues from smart stem cells that precisely respond to their environment opens an exciting area of investigation for regenerative medicine.”
Dr. Guilak is a professor at Washington University Department of Orthopedic Surgery and is Director of Research for Shriners Hospitals for Children in St. Louis. He is also the co-director of the Washington University Center of Regenerative Medicine and has appointments in the Departments of Developmental Biology and Biomedical Engineering. He has received funding from the Arthritis Foundation for three separate projects over the past 10 years.