Embryonic Stem Cell-Derived Chondroprogenitor Cells to Repair Osteochondral Defects

Surgical approaches to the treatment of focal cartilage defects can be classified into repair, replacement, and regeneration therapies. Marrow stimulation procedures such as microfracture result in a repair tissue that is predominantly fibrocartilaginous in nature, which is mechanically less durable than articular cartilage and survives on average 7 years before requiring another procedure. Osteochondral grafting (autologous or allogeneic) replaces the defect with fresh mature cartilage and bone. While the tissue replicates natural cartilage, the grafted cartilage does not integrate or bond with the host tissue. Autologous chondrocyte implantation (ACI) attempts to regenerate tissue by injecting chondrocytes into the defect. Results with this technique are mixed with several randomized clinical trials failing to find a clinically and statistically significant benefit over microfracture or other procedures.
Our approach is to advance third-generation cell therapy by constructing scaffolds that are seeded with chondroprogenitor cells programmed to undergo differentiation into bone and cartilage cells. If successful, this will be the first-in-man embryonic stem-cell-based treatment of an orthopaedic disease that has challenged repeated attempts over the last 400 years. The product has the unique advantage that the same material is universally applicable in all patients with a range of different defect shapes and sizes. The preclinical development, characterization, efficacy, and safety will also support and advance stem-cell-based regenerative medicine in general.