CRISPR-Modified Mesenchymal Stromal Cells Show Therapeutic Potential in Osteoarthritis

In an article published in Molecular Therapy, researchers at Rush University Medical Center in Chicago report that simultaneous Sox9 activation and RelA inhibition using a catalytically-dead Cas9 resulted in engineered mesenchymal stromal cells with enhanced cartilage-forming potential and downregulated inflammatory responses.

By: Karen O'Hanlon Cohrt - Jun. 18, 2024
News

The work, led by Jian Huang PhD, who is an Assistant Professor in Orthopedic Surgery at Rush University, was motivated by efforts to develop better mesenchymal stromal cell (MSC) preparations to treat osteoarthritis (OA), a painful and debilitating disease that affects more than 500 million people worldwide. Injection of MSCs directly into the affected joints has shown promise for the treatment for OA, but this appraoch is hampered by inconsistencies in the MSC cell preparations, which makes it difficult to optimise treatment and challenges the proper evaluation of clinical benefit.

To address those challenges, the team hypothesised that the expression levels of both Sox9, which regulateschondrocyte proliferation and differentiation, and RelA, which promotes proliferation but inhibits osteogenic and chondrogenic differentiation, could be fine-tuned to augment the chondrogenic and immunomodulatory potentials of the cells. The found that intra-articular delivery (into the joints) of catalytically-dead Cas9 (dCas9)-engineered cells significantly reduced cartilage degradation and relieved pain associated in an OA disease model. Further experiments to characterise the modified cells revealed that they promoted the expression of factors known to be beneficial for cartilage integrity, inhibited the production of catabolic enzymes in osteoarthritic joints, and suppressed inflammation. They also report that a substantial number of modified MSCs could survive in the cartilaginous tissues including articular cartilage and meniscus.

Read the full article in Molecular Therapy here.

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News: CRISPR-Modified Mesenchymal Stromal Cells Show Therapeutic Potential in Osteoarthritis
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