Arthritis Vaccine Could Emerge From Stem Cell Technology


Mouse stem cells could have just helped with the answer to solving chronic diseases.

The stem cells are created through gene-editing technology and are known as stem cells modified for autonomous regenerative therapy, or SMART cells. The newly-edited cells are being used to treat inflammation with a goal of pinpointing localized pain, said Farshid Guilak, senior author and professor of Orthopedic Surgery at Washington University School of Medicine.

This patient has arthritis in the thumb. Credit: handarmdoc/Flickr, CC BY 2.0

“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,” Guilak said in a press release. “To do this, we needed to create a ‘smart’ cell.”

The study authors said that genetic engineering can be used to rewire cell circuits in order to specifically change the relationships between inflammatory mediators and their antagonists. The engineering helps to provide a foundation for cell-based drug delivery that speeds up the rate at which a vaccine can start working.

“We want to use our gene-editing technology as a way to deliver targeted therapy in response to localized inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body,” Guilak said. “If this strategy proves to be successful, the engineered cells only would block inflammation when inflammatory signals are released, such as during an arthritic flare in that joint.”

Related: Scientists Grow Beating Heart Cells on Spinach Leaves

Mouse cells were grown and used in the study to test the gene-editing technology. The researchers were able to replace an inflammation mediator with a drug that suppresses the body’s response to inflammation response, known as a TNF-alpha inhibitor, using CRISPR technology.

“Exploiting tools from synthetic biology, we found we could re-code the program that stem cells use to orchestrate their response to inflammation,” said Jonathan Brunger, the study’s first author and a postdoctoral fellow in Cellular and Molecular Pharmacology at the University of California, San Francisco. “We hijacked an inflammatory pathway to create cells that produced a protective drug.”

These are photomicrographs of stained tissue sections from engineered cartilage samples in the study. Credit: Brunger, Zutshi, Willard, Gersbach, and Guilak/Stem Cell Reports

The team also coded cells that lit up when responding to inflammation, so they could determine which cells needed attention. The stem cells have the potential to help with several different health issues, Guilak said.

“When these cells see TNF-alpha, they rapidly activate a therapy that reduces inflammation,” Guilak said. “We believe this strategy also may work for other systems that depend on a feedback loop. In diabetes, for example, it’s possible we could make stem cells that would sense glucose and turn on insulin in response. We are using pluripotent stem cells, so we can make them into any cell type, and with CRISPR, we can remove or insert genes that have the potential to treat many types of disorders.”

The autoregulation that the stem cells can provide has the possibility to help treat diseases early, before symptoms become serious health issues, the study said. The possibilities are exciting, Brunger added.

“The ability to build living tissues from ‘smart’ stem cells that precisely respond to their environment opens up exciting possibilities for investigation in regenerative medicine,” Brunger said.

Related: Dairy-Free Diets Could Harm Young People’s Bone Health