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A combined developmental cell biology and tissue engineering approach to repair the articular surface of synovial joints

Periodic Reporting for period 1 - ReSurface (A combined developmental cell biology and tissue engineering approach to repair the articular surface of synovial joints)

Reporting period: 2019-08-01 to 2021-07-31

Articular cartilage is found lining our joints and allows for smooth joint movement. If it becomes damaged, the resident cells, articular chondrocytes (ACs), are unable to repair the damage. Instead, a progressive degradation of the tissue begins, eventually developing into osteoarthritis. Osteoarthritis affects approximately 10-12% of the adult population, causing pain, stiffness, and inflammation and thus severely impacting quality of life. Early treatment of articular cartilage lesions may correct disease progression; however suitable treatments with long-term efficacy remain elusive, due to gaps in our knowledge of how this type of cartilage develops prenatally, and how it is maintained postnatally. Therefore, there is a critical need to develop methods to study articular cartilage development to inform new regenerative therapies. The overall goal of ReSurface is to develop methods to study human articular cartilage development using human pluripotent stem cells (hPSCs). By figuring out how these cells become articular chondrocytes, and later maintain articular cartilage tissue, we can find out what controls human articular cartilage production and what cells are safe and suitable for articular cartilage repair, or find out if there are drug therapies that can stimulate repair.
We have developed a method to generate stable articular cartilage tissue in a dish using human pluripotent stem cells. Under defined conditions, these cells can produce cartilage tissue which closely resembles healthy adult cartilage tissue. Using this protocol, we can now study cartilage development over time, gaining a deeper understanding of how the cells produce cartilage tissue and how they respond to injury or aging.
The research already completed during ReSurface is critical to move the field beyond the current state-of-the-art as several recent systematic reviews have determined that current cell-based therapies for articular cartilage repair are inadequate. Furthermore, with an aging population, the incidence of OA is only set to increase and this project is closely aligned with the EU Framework for Research and Innovation for personalizing healthcare by understanding mechanisms of development, improving our ability to manage disease, and to demonstrate new tools for disease management. Through this project we are now able to closely study human joint development for the first time. We have developed a reproducible protocol for deriving stable articular chondrocytes from hPSCs, cells which produce articular cartilage tissue that appears very similar to healthy native human cartilage. The cells themselves have potential as a treatment for articular cartilage defects caused by trauma, which may in turn inhibit the progression of osteoarthritis. Furthermore, we have also generated a single cell RNA-seq dataset capturing the cellular dynamics of developing cartilage. This work will potentially lead to the identification of new drug-based therapies that can stimulate articular cartilage regeneration in situ, without the requirement of surgery. The successful treatment of articular cartilage defects would limit pain and suffering for patients which would subsequently have socioeconomic benefits by limiting loss of wages caused by time away from work and promote healthy and active aging.
Successful production or cartilage tissues from hPSCs