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New UCLA study could reverse damage to joints

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A new study by UCLA stem cell researchers could lead to the growth of new articular cartilage; thus, avoiding the need for joint replacement surgery with artificial materials. They published their findings on published online on December 12 in the journal Stem Cell Reports.

The stem cell researchers at UCLA’s Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have identified the origin of––and tracked the development of––cells that develop into human articular cartilage. They note that their study provides what could be a new cell source and biological roadmap for treatments to repair cartilage defects and osteoarthritis. They note that clinical trials on humans could begin within three years.

Currently, osteoarthritis affects more than 20 million individuals in the US alone; thus, making joint surface restoration a major concern of modern medicine. Articular cartilage is a highly specialized tissue, which develops from cells known as chondrocytes; this tissue protects the bones of joints from forces related to load bearing and impact; it allows almost frictionless motion between the joint surfaces. Cartilage injury and lack of cartilage regeneration frequently results in osteoarthritis involving deterioration of joints, including cartilage and bone.
Different cell types have been studied in regard to their ability to generate articular cartilage; however, none of the current cell-based repair strategies have generated long-lasting articular cartilage tissue in the laboratory.

The researchers note that the combination of developmental biology and tissue engineering that their study involved could provide scientists with checkpoints to tell if the chondrocytes are developing properly. “We began with three questions about cartilage development,” explained lead researcher Dr. Denis Evseenko, assistant professor of orthopedic surgery and head of UCLA’s Laboratory of Connective Tissue Regeneration. He added, “We wanted to know the key molecular mechanisms, the key cell populations, and the developmental stages in humans. We carefully studied how the chondrocytes developed, watching not only their genes, but other biological markers that will allow us to apply the system for the improvement of current stem cell-based therapeutic approaches.”

The study authors note that their research was also the first attempt to generate all the important landmarks, which allow generation of clinically relevant cell types for cartilage regeneration with the highest animal-free standards. Thus, the process did not depend upon on any animal components. As a result, therapeutic products such as stem-cell serums can be produced that are safe for humans.

Dr. Evseenko noted that in a living organism more than one cell type is responsible for tissue regeneration; therefore, in addition to the studies involving generation of articular cartilage from human stem cells, his team is now testing different protocols using different combinations of adult progenitor cells present in the joint to regenerate cartilage until the best one is found for therapeutic use. Now that these progenitor cells and the landmarks of proper cartilage development have been identified, Dr. Evseenko is confident that an effective cellular therapy for diseased or damaged joint cartilage could be tested in human trials within three years. He explains that such stem cell-based therapies could make many current knee and hip replacement surgeries unnecessary; as a result, patients could regrow lost cartilage, keep their bones intact, and avoid the discomfort and risk of major joint-replacement surgery.

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