European Journal of Radiology 57 (2006) 32–36 Lineage plasticity and cell biology of fibrocartilage and hyaline cartilage: Its significance in cartilage repair and replacement Anthony J. Freemont ∗ , Judith Hoyland Regenerative Medicine Research Group, University of Manchester, England, UK Received 12 August 2005; received in revised form 15 August 2005; accepted 16 August 2005 Abstract Cartilage repair is a major goal of modern tissue engineering. To produce novel engineered implants requires a knowledge of the basic biology of the tissues that are to be replaced or reproduced. Hyaline articular cartilage and meniscal fibrocartilage are two tissues that have excited attention because of the frequency with which they are damaged. A basic strategy is to re-engineer these tissues ex vivo by stimulating stem cells to differentiate into the cells of the mature tissue capable of producing an intact functional matrix. In this brief review, the sources of cells for tissue engineering cartilage and the culture conditions that have promoted differentiation are discussed within the context of natural cartilage repair. In particular, the role of cell density, cytokines, load, matrices and oxygen tension are discussed. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Cartilage; Fibrocartilage; Injury; Repair 1. Background In the human body hyaline and fibrocartilage are found mainly within the skeleton, and then predominantly in and around joints. As their name would suggest, these two tissues can be distinguished by the appearances of their matrices. To fully understand the implications of the differences between the matrices, it is necessary to consider a third tissue which is “pure” fibrous tissue. 2. The structure of fibrous tissue, fibrocartilage and hyaline cartilage Fibrous tissue matrix consists almost entirely of the fibrous molecule type I collagen. The collagen fibre bundles are very highly organised usually in parallel arrays. It is this organ- isation that gives the tissue strength in tension. Apparently, ∗ Corresponding author at: Regenerative Medicine Research Group, DLRM, Stopford Building, Manchester University, Oxford Road M13 9PT, UK. Tel.: +44 161 275 5269; fax: +44 161 275 5268. E-mail address: Tony.freemont@man.ac.uk (A.J. Freemont). randomly scattered through the collagenous matrix are the cells of the fibrous tissue—fibroblasts (Fig. 1a). Fibroblasts are spindle shaped. These cells are not in direct contact with one another, but are rather completely surrounded by matrix to which they attach cell adhesion molecules called integrins which recognise specific amino acid sequences on the matrix molecules. These sequences consist of four amino acids – Arg-Gly-Asp-Ser – and are known as the RGDS motif. Hyaline cartilage also contains a fibrilar collagen, but one with different components known as type II collagen. It has a second major class of matrix molecules, the proteoglycans, the most common of which is called aggrecan. Scattered through the chondroid matrix are the cells of cartilage, known as chondrocytes (Fig. 1b). These are similar, in many respects to fibroblasts, but have a rounded morphology. Hyaline car- tilage is subjected to very high compressive loads and there is a risk that the cells may be irreversibly compressed. The cells have adapted to this by developing a unique component of the matrix around themselves. This is known as the chon- drocyte domain. It consists of a rounded space known as the chondrocyte lacune surrounded by a specialised region of the cartilage known as the domainal region. The domainal region of the cartilage is rich in type VI collagen. It forms a spheri- cal structure around the cell that in many respects resembles 0720-048X/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2005.08.008