A joint effort to understand cartilage development

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Credit: Ben Van Handel/Denis Evseenko Lab/USC Stem Cell

Anyone with arthritis can appreciate how useful it would be if scientists could grow cartilage in the lab. To this end, Keck School of Medicine of USC scientists in the USC Stem Cell laboratory of Denis Evseenko, MD, PhD, collaborated with colleagues at several institutions to provide new insights into how gene activity drives the development of cartilage. Their findings appear today in Nature Communications.

Based on their molecular studies, the scientists identified and characterized, for the first time, unique cell populations that form the superficial zone of human joint cartilage. The superficial zone plays the most critical role in cushioning the joint, and is often partially or completely lost in arthritis.

"Our results not only offer a unique molecular atlas of human skeletal development, but also define a strategy for joint cartilage repair," says Evseenko, who is the study's corresponding author and an associate professor of orthopaedic surgery, and stem cell biology and regenerative medicine at the Keck School.

In a series of experiments, Gabriel B. Ferguson, PhD, postdoctoral scholar – research associate, Ben Van Handel, PhD, postdoctoral scholar – research associate, and colleagues compared the gene activity of developing human cartilage cells with several other cell types.

First, they compared the cartilage cells to four other types of developing human cells: the precursors to bone, muscle, tendon and ligament. As the cartilage matured, the genes specific to cartilage became increasingly active, while genes related to the other cell types became repressed.

Next, the scientists compared these developing human cartilage cells to equivalent cells from mice. The team found many broad similarities in gene activity.

The researchers also carried out a detailed comparison of ordinary human cartilage cells and stem cell-derived human cartilage cells, taking into account genetics, genetic regulation and function. The researchers demonstrated that stem cell-derived cartilage does not fully develop in the Petri dish but rather retains the genetic hallmarks typical of fetal cartilage. However, if the scientists transplanted stem cell-derived human cartilage at a particular stage of development into an arthritic rat, the cartilage would lose its fetal hallmarks and fully mature — regenerating the critical superficial zone.

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About USC Stem Cell

USC Stem Cell is a collaborative, multidisciplinary effort working to translate the potential of stem cell research to the clinical imperative of regenerative medicine. Centered at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, the initiative brings together researchers and clinicians from USC and Children's Hospital Los Angeles.

About the Keck School of Medicine of USC

Founded in 1885, the Keck School of Medicine of USC is among the nation's leaders in innovative patient care, scientific discovery, education and community service. It is part of Keck Medicine of USC, the University of Southern California's medical enterprise, one of only two university-owned academic medical centers in the Los Angeles area. This includes Keck Medical Center of USC, composed of Keck Hospital of USC and USC Norris Cancer Hospital. The two world-class, USC-owned hospitals are staffed by more than 500 physicians who are faculty at the Keck School. The school has more than 1,750 full-time faculty members and voluntary faculty of more than 2,400 physicians. These faculty direct the education of approximately 800 medical students and 1,000 students pursuing graduate and postgraduate degrees. The school trains more than 900 resident physicians in more than 50 specialty or subspecialty programs and is the largest educator of physicians practicing in Southern California. Together, the school's faculty and residents serve more than 1.5 million patients each year at Keck Hospital of USC and USC Norris Cancer Hospital, as well as USC-affiliated hospitals, Children's Hospital Los Angeles and Los Angeles County + USC Medical Center. Keck School faculty also conduct research and teach at several research centers and institutes, including the Eli and Edythe Broad Center for Stem Cell Research and Regenerative Medicine at USC, USC Cardiovascular Thoracic Institute, USC Institute of Urology, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, USC Norris Comprehensive Cancer Center, USC Roski Eye Institute and Zilkha Neurogenetic Institute.

In 2018, U.S. News & World Report ranked the Keck School among the top 35 medical schools in the country.

For more information, go to keck.usc.edu.

This study was supported by the National Institutes of Health under award number R01AR071734, the U.S. Department of Defense under award number W81XWH-13-1-0465 and the California Institute for Regenerative Medicine under award numbers RB5-07230-B and TRAN1-09288. Approximately 50 percent of the project's funding was federally funded. Fifty percent of the project's funding was not federally funded. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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