Science Sub-Journal: Treatment of rheumatoid arthritis with drug-releasing implanted cells

Researchers at Washington University School of Medicine in St.

In a mouse model of rheumatoid arthritis, these engineered cells reduced inflammation and prevented a type of bone damage called bone erosion

"Doctors often use injections or injections of anti-inflammatory biological drugs to treat patients with rheumatoid arthritis, but when these drugs are used long enough and in large enough doses, significant side effects can occur," said senior researcher Dr.

The new discovery was published online in the journal "Science Advances" on September 1

Researchers use CRISPR-Cas9 genome editing technology to make cells secrete biological drugs to deal with inflammation

Gilak is the co-director of the Center for Regenerative Medicine at the University of Washington.

His laboratory also used CRISPR-Cas9 technology to construct so-called SMART chondrocytes (stem cells for autonomous regeneration therapy).

In this new study, Gilak’s team combined these strategies to provide treatments for rheumatoid arthritis

"These cells stay in the skin or joints for several months, and when they sense an inflammatory environment, they release a biological drug," said Guilak, who is also the director of research at Shriners Children's Hospital in St.

In this case, the drug is similar to the immunosuppressive drug anakinra, which binds to IL-1 and blocks its activity

"We focus on bone erosion because it is a big problem for patients with rheumatoid arthritis, and current biological agents are not effective in treating rheumatoid arthritis," said co-first author Yunrak Choi, MD, who is the Guilak experiment Plastic surgeon in the room

Gilak collaborated with Christine Pham, MD, Director of the Rheumatology Department, Gay and Ira May Magnes Professor of Medicine

Pham explained: "Although biological agents have completely changed the treatment of inflammatory arthritis, continued use of these drugs often leads to adverse events, including increased risk of infection

Through CRISPR-Cas9 gene editing, cells have the potential to be programmed to make a variety of drugs, which means that if one arthritis drug is better than another in a particular patient, researchers can design cartilage cells to Carry out personalized treatment

"Many arthritis patients have to take these drugs and inject themselves every day, every week or every two weeks, while others go to the doctor's office to receive one of these biological agents injected every few months, but in this study, we have It proved that we can live tissue into a drug delivery system," said Kelsey H.
Collins, Ph.
D.
, a postdoctoral researcher in Gilac’s laboratory and one of the first authors of this study
.
These cells can sense problems and respond by producing drugs
.
This approach also helps us understand why certain biological agents have limited effects on inflammatory arthritis
.
This is not because they are not binding to the correct target, but it may be because the injected drugs have a shorter lifespan compared to the level of drug release that is automatically controlled by implanted SMART cells
.
"

Researchers are continuing to experiment with CRISPR-Cas9 and stem cells, and even engineered cells, which may produce more than one drug in response to different triggers of inflammation
.

Original title:

A genome-engineered bioartificial implant for autoregulated anticytokine drug delivery