Edited stem cells could vaccinate against arthritis

Researchers use CRISPR technology to edit stem cells which have the potential to become a vaccine for arthritis.

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May 08, 2017

Researchers from Washington University School of Medicine and Shriners Hospitals for Children-St. Louis (both MO, USA), in collaboration with investigators at Duke University and Cytex Therapeutics Inc. (both NC, USA), have used CRISPR technology to rewire stem cells so that they could potentially act as a vaccine for arthritis. The research was recently published in Stem Cell Reports.

Current drugs used to treat arthritis are given systematically and attack an inflammation-promoting molecule called tumor necrosis factor (TNF)-alpha. This means they can interfere with the patients’ immune system.

"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," commented the papers senior author Farshid Guilak (professor of orthopedic surgery, Washington University School of Medicine). "To do this, we needed to create a 'smart' cell."

SMART cells (Stem cells Modified for Autonomous Regenerative Therapy) are created by removing a key gene in the inflammatory process and replacing it with a gene that releases a biologic drug that combats inflammation. The SMART cells will develop into cartilage cells that, ideally, will replace arthritic cartilage and simultaneously protect the synthetic cartilage cells created by Guilak's team, the natural cartilage cells and other tissues from the damage that occurs with chronic inflammation.

"When these cells see TNF-alpha, they rapidly activate a therapy that reduces inflammation," explained Guilak. "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 ability to build living tissues from 'smart' stem cells that precisely respond to their environment opens up exciting possibilities for investigation in regenerative medicine," concluded Guilak.

Written by Adam Tarring

Source: Brunger JM, Zutshi A, Willard VP, Gersbach CA, Guilak F. Genome Engineering of Stem Cells for Autonomously Regulated, Closed-Loop Delivery of Biologic Drugs. Stem Cell Reports. doi: 10.1016/j.stemcr.2017.03.022 (2017) (Epub ahead of print); https://www.sciencedaily.com/releases/2017/04/170427141703.htm

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Go to the profile of James L. Sherley, M.D., Ph.D.

An exciting therapeutic paradigm and prospect, but the report has the common deficiency of not considering the impact of tissue cell turnover. However, in the particular case of chondrocytes, this implicit oversight may not be as consequential for the planned therapeutic strategy, as chondrocyte turnover rates measured in animal articular cartilage are on the order of several years. So, in this special case, failure to use long-term asymmetrically self-renewing distributed stem cells (DSCs; and more specifically cartilage DSCs) as the carriers of the elegant auto-regulated inflammation reduction system may be both a practical and an effective therapy design - provided, of course, that the proposed iPSC-derived differentiated cells also prove to have inconsequential rates of tumor formation.

James L. Sherley, M.D., Ph.D.
Asymmetrex, LLC

Go to the profile of Freya Leask
Freya Leask over 2 years ago

Thanks for your insightful comments as always, James - does anyone else agree or disagree?

Go to the profile of Edward Loniewski
Edward Loniewski over 2 years ago

Excellent idea and just another exciting application for CRISPR technology. However, this would only address one pathway and we all know that (TNF)-alpha is needed for normal joint homeostasis and complete suppression may have some unforeseen consequences. It is the unregulated increase in (TNF)-alpha which causes the activation of just a few catabolic pathways. It appears that IL-1B may be a more logical choice since this is involved in so many critical catabolic pathways and inhibition of TGF -B . Inhibition of IL-1B may be the key rather than TNF. However, there is probably some step in this process I am missing. Otherwise this is a great idea with great potential for future treatment of some of my patients suffering from arthritis everyday.