REVIEW www.nature.com/clinicalpractice/rheum Technology Insight: adult stem cells in cartilage regeneration and tissue engineering Faye H Chen, Kathleen T Rousche and Rocky S Tuan* INTRODUCTION Osteoarthritis (OA) and related degenerative joint diseases result in a heavy disease burden and affect millions of people annually. 1 Once damaged, articular cartilage lacks the ability to properly repair and regenerate itself. Various surgical interventions and procedures are used to relieve pain and restore joint function. Relatively minimal procedures include lavage, shaving, laser abrasion, and microfracture of the subchondral bone. More extensive surgical procedures include autogenic or allogenic osteochondral transplanta- tion, autologous perichondral and periosteal grafts, and autologous chondrocyte implanta- tion. 2 The drastic procedure of total joint replace- ment remains the treatment of choice today for extensive lesions or joint destruction. Other than total joint replacement, which has inherent risks and a finite life expectancy, these procedures, although successful to varying degrees in treating articular defects, are effective only for chondral defects of limited sizes. Availability of tissue graft material and donor site morbidity remain the major challenges. 2 There is a need, therefore, for improved cartilage-repair modalities and engineered-tissue constructs that are suitable for transplantation. The use of chondrocytes in cartilage tissue engineering has been restricted by the limited availability of these cells and their intrinsic tendency to lose their phenotype during expansion. Adult stem cells, because of the ease with which they can be isolated, their capacity to self-replicate, and their ability to differentiate along multiple connective-tissue lineages, have become the cell type of choice for cartilage tissue engineering. In this review, the current knowl- edge of cartilage tissue engineering and regenera- tion is summarized. We first review the structure and function of cartilage, as a foundation to guide cartilage tissue engineering and regenera- tion. This is followed by a description of the components that are critical for cartilage tissue engineering, and a discussion of the advantages of using adult stem cells for this process. Factors and signaling molecules that are important for Articular cartilage, the load-bearing tissue of the joint, has limited repair and regeneration potential. The scarcity of treatment modalities for large chondral defects has motivated attempts to engineer cartilage tissue constructs that can meet the functional demands of this tissue in vivo. Cartilage tissue engineering requires three components: cells, scaffold, and environment. Adult stem cells, specifically multipotent mesenchymal stem cells, are considered the cell type of choice for tissue engineering, because of the ease with which they can be isolated and expanded and their multilineage differentiation capabilities. Successful outcome of cell-based cartilage tissue engineering ultimately depends on the proper differentiation of stem cells into chondrocytes and the assembly of the appropriate cartilaginous matrix to achieve the load-bearing capabilities of the natural articular cartilage. Multiple requirements, including growth factors, signaling molecules, and physical influences, need to be met. Adult mesenchymal stem-cell-based tissue engineering is a promising technology for the development of a transplantable cartilage replacement to improve joint function. KEYWORDS adult stem cell, cartilage, regeneration, repair, tissue engineering FH Chen is a staff scientist, KT Rousche is a postdoctoral fellow and RS Tuan is Chief of the Cartilage Biology and Orthopaedics Branch, at the National Institute of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. Correspondence *Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Building 50, Room 1523, 50 South Drive, MSC 8022, Bethesda, MD 20892-8022, USA tuanr@mail.nih.gov Received 26 October 2005 Accepted 28 March 2006 www.nature.com/clinicalpractice doi:10.1038/ncprheum0216 REVIEW CRITERIA PubMed was searched for articles published up to 3 March 2006. Search terms used were “stem cell” in combination with “cartilage tissue engineering”, “cartilage regeneration”, and “cartilage repair”. Abstracts were reviewed, and full articles were retrieved on relevant references. SUMMARY JULY 2006 VOL 2 NO 7 NATURE CLINICAL PRACTICE RHEUMATOLOGY 373 Nature Publishing Group ©2006