Growing cartilage for human replacement—where are we?

Abstract

Articular cartilage injuries predispose to osteoartritis development in the joint and the intrinsic repair capacity of adult hyaline cartilage is limited. Over the years, several surgical techniques have been introduced to improve the repair of injured articular cartilage surfaces, but articular cartilage resurfacing remains a scientific challenge. The use of cultured autologous chondrocytes in patients with cartilage injuries have shown encouraging clinical results in combination with the regeneration of hyaline cartilage [1]. This work started with animal studies in the US in the 1980s [2] and continued in Gothenburg, Sweden, with research on human articular chondrocytes and the potential use in human cell therapy. At that time, other chondrogeneic cells such as auricular chondrocytes, nasal chondrocytes, rib perichondrial cells, allogeneic chondrocytes or mesenchymal bone marrow stromal cells could have been alternative cell sources, but the clinical reality was the driving force behind the decision to use articular cartilage. Since the clinical diagnosis is conducted by arthroscopic inspection and thus the surgeon has sterile access to the joint cavity, there is an opportunity to harvest cartilage conveniently. Other sources of cartilage were less likely to be used, either for practical reasons that other areas of the body had to be cleaned and sterilized (e.g. rib cartilage) or due to the fact that donor site morbidity would give the patient additional suffering. The reason for the in vitro chondrocyte culture is to increase the cell number from an original few 100,000 to several million cells. Chondrocytes are isolated from small slices of cartilage harvested transarthroscopically from a minor weight-bearing area in the injured knee. The amount of cartilage harvested is only a few hundred milligrams. The extracellular matrix is removed from the cartilage by enzymatic digestion and the average cell yield is between 2,000 and 3,000 cells/mg biopsy weight; subsequently, cells are expanded in monolayer culture in a defined cell culture medium with a 10% addition of the patient’s own serum. The knowledge gained over the years has demonstrated that during the expansion of chondrocytes in vitro there is a selection of a limited number of chondrocyte progenitor clones and the culture process allows the cells to revert to a more primitive foetal stage through a process of dedifferentiation. Interestingly, the cellular gene programme activated during the redifferentiation process is similar to programs controlling chondrogenesis in foetal life [3]. Once a suitable number of cells has been reached, the increased number of chondrocytes are suspended in culture medium and then implanted into the area of cartilage defect using a periosteal patch over the defect as a method of cell containment. The closed compartment initiates a process of cell condensation and cartilage neo-formation similar to the mesenchymal condensation seen in the foetal stage of limb formation.