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Lending Regeneration a Helping Hand - New research suggests TGF-B allows cultured chondrocytes to redifferentiate

June 23, 2017


Formation of Hyaline Cartilage Tissue by Passaged Human Osteoarthritic Chondrocytes

By Meghan Krizus

  Author Vanessa Bianchi (left), is investigating how to redifferentiate chondrocytes into functional cartilage, able to be grown on bone substitute (right).

Author Vanessa Bianchi (left), is investigating how to redifferentiate chondrocytes into functional cartilage, able to be grown on bone substitute (right).

According to the Arthritis Society, over three million Canadian suffer from osteoarthritis. This disease affects the cartilage of joints between bones, causing it to break down and resulting in pain, stiffness, and swelling in affected joints, as well as a reduction in the quality of life of sufferers. Moreover, this disease is not only progressive and debilitating, but also currently incurable. While treatments aimed at alleviating symptoms exist, there is a dire need for therapies that can regenerate lost cartilage. For this reason, repairing cartilage damaged by diseases like osteoarthritis, or lifestyle factors such as sports injury, is the focus of a recent publication and continuing research at the LTRI.

In ongoing work from the Kandel lab, researchers investigate how cartilage can be grown in vitro to replace tissue lost to injury or disease. Damaged “cartilage doesn’t regenerate,” explains researcher Vanessa Bianchi. “That’s the main problem…there’s really no cure.” So Bianchi and her collaborators seek to regenerate in vitro a specific form of cartilage: articular cartilage, itself a form of hyaline cartilage. As articular cartilage makes up the joints between bones, this tissue is of particular interest to those looking to find treatments for diseases like osteoarthritis.

In a recent publication, researchers use chondrocytes, the cells that make up cartilage, to grow functional articular cartilage in cell culture. This work solves a key issue in the culture of chondrocytes: that in previous attempts to make tissue from passaged chondrocytes, these cells dedifferentiated, making them no longer able to form articular cartilage.

This paper provides strong evidence that this dedifferentiation can be overcome by redifferentiating passaged chondrocytes. While redifferentiation has been attempted in previous studies, these studies have had severe limitations. The authors of this work pinpointed TGFΒ3, one of the isoforms of transforming growth factor beta, as a promising factor in encouraging redifferentiation as among its many functions, TGFΒ has been shown to play significant roles in cell differentiation and repair of articular cartilage.

This study revealed that cultured human chondrocytes, when supplemented with TGFΒ3, showed higher levels of two of the primary components of articular cartilage (collagen type 2, and highly sulfated proteoglycan aggrecan), than cells not supplemented. Perhaps even more interestingly, even after TGFΒ supplementation was stopped, chondrocytes maintained their structure. This is a particularly noteworthy finding given that if used to replace a patient’s damaged cartilage, implanted chondrocytes would no longer be able to be supplemented with TGFΒ.

This work provides a promising first step toward a clinical treatment and provides the foundation for the next steps toward an in vivo cure for damaged cartilage. According to Bianchi, such research is already underway, and she and her collaborators have begun in vivo work with animal models.

Bianchi also stresses the importance of collaboration between the bench and the bedside. “It’s definitely important to start with animal cells,” she says. “But I think it’s really important…to try to work with physicians.” In this project, researchers at the LTRI collaborated not only with the clinical departments of Orthopaedics and of Pathology and Laboratory Medicine here at Mount Sinai Hospital, but with researchers at institutions such as St. Michael’s Hospital—just another example of how the LTRI’s collaborative brand of research paves the way toward medical innovation.

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