Researchers at Shriners Hospitals for Children in St. Louis, and the Washington University School of Medicine, have used CRISPR gene editing to engineer stem cells capable of producing an anti-inflammatory arthritis vaccine. The cells – dubbed, stem cells modified for autonomous regenerative therapy (SMART) – could provide safer, more effective treatment options for patients with a range of chronic conditions.
As with many chronic inflammatory and autoimmune diseases, medications for arthritis are taken at regular intervals, and at relatively high doses, to prevent symptoms associated with the condition. In comparison, genome-engineered SMART cells are designed to respond to localized inflammation by releasing biologic drugs in an autonomous manner.
These SMART cells are currently still in the preclinical phase, and the technique has only been applied to mouse-derived stem cells. The researchers published their work in the journal, Stem Cell Reports.
“For children with juvenile arthritis, this breakthrough could have significant benefits as many of the current treatment options cause unwanted side effects and may not be appropriate for children,” said senior author Dr. Farshid Guilak, director of research for the St. Louis Shriners Hospital and professor of orthopedic surgery at Washington University School of Medicine. “Our goal is to deliver a therapy that is self-regulating and targeted specifically to inflammation in a particular joint, as opposed to current drug therapies that impact the immune response throughout the entire body.”
According to Guilak and his colleagues, chronic diseases like arthritis are characterized by the over-activity of pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1). Using CRISPR gene editing, the researchers successfully generating stem cells capable of detecting inflammation and releasing a therapeutic – produced by expression of a transgene – in response to the stimulus.
“The autoregulated nature of this approach may allow for therapeutic delivery during early, possibly pre-symptomatic stages of diseases, effectively providing the potential for biologic cell-based vaccines for autoimmune diseases,” wrote the authors in the research article. “The customization of intrinsic cellular signaling pathways in therapeutic stem cell populations, as demonstrated in this work, opens innovative possibilities for safer and more effective treatments applicable to a wide variety of diseases.”