StemCell Therapy

By Staff.

Researchers are editing stem cells in an effort to fight arthritis with the goal of possibly creating a vaccine that targets inflammation in joints.

Theyve been successful in rewiring mouse stem cells to fight inflammation caused by arthritis and other chronic conditions. These stem cells, known as SMART (Stem cells Modified for Autonomous Regenerative Therapy), develop into cartilage cells that produce anti-inflammatory drug that may replace arthritic cartilage and protect joints from additional damage.

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, said Farshid Guilak, PhD, the papers senior author and a professor of orthopedic surgery at Washington University School of Medicine. To do this, we needed to create a smart cell.

Many current drugs used to treat arthritis like Enbrel, Humira and Remicade, attack an inflammation-promoting molecule called tumor necrosis factor-alpha (TNF-alpha). These drugs are given systemically rather than targeted to joints, which can lead to various unwanted side effects.

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 added. 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.

The researchers also encoded the stem/cartilage cells with genes that made the cells light up when responding to inflammation, so the scientists could tell when the cells were responding. Recently, Guilaks team has begun testing the engineered stem cells in mouse models of rheumatoid arthritis and other inflammatory diseases.

If the work can be replicated in animals and then developed into a clinical therapy, the engineered cells or cartilage grown from stem cells would respond to inflammation by releasing a biologic drug the TNF-alpha inhibitor that would protect the synthetic cartilage cells that Guilaks team created and the natural cartilage cells in specific joints.

When these cells see TNF-alpha, they rapidly activate a therapy that reduces inflammation, Guilak explained. We believe this strategy also may work for other systems that depend on a feedback loop. In diabetes, for example, its 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 we can remove or insert genes that have the potential to treat many types of disorders.

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, said Jonathan Brunger, PhD, the papers first author and a postdoctoral fellow in cellular and molecular pharmacology at the University of California, San Francisco.

The research was published in the journalStem Cell Reports.

More:
Can An Arthritis Vaccine Be In Our Future? - National Pain Report

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