Engineering cartilage and bone using human mesenchymal stem cells

Cartilage and bone defects are leading causes of disability. The economic burden of orthopedic repair exceeds 28 billion dollars per year in the United States alone,1 and the situation is similar in many other countries. Although artificial joints or metal inserts are widely utilized and in most cases work well, cell-based therapies based on tissue-engineered cartilage and bone beckon a new frontier for clinical treatment owing to their biocompatibility and long-term prognosis. Functional tissue engineering2 involves an integrated use of three components — cells, scaffold material, and a bioreactor (Fig. ​(Fig.1),1), — in settings that mimic some elements of the in vivo environment. Synergistic interactions of biomimetic cues applied with temporal and spatial regulation influence cell growth and biosynthesis and guide cellular development into functional replacement tissue constructs. This article discusses the design criteria and parameters essential for engineering cartilage and bone grafts as well as the current status and future perspective of the field. Fig. 1 Main components of tissue engineering Tissue engineering Cells Cells are the actual “tissue engineers,” and several considerations guide the choice of cell sources. The cells are ideally immunocompatible, such as autologous chondrocytes for cartilage repair. The use of chondrocytes, however, is limited by their availability and their capacity for expansion in culture, as well as the need for a separate surgery to harvest the cells. The proliferative characteristics of autologous adult mesenchymal stem cells (MSCs) and the less invasive procedures for their procurement are thus considered important advantages. Although MSCs have better expandability than differentiated cells, extensive expansion is known to decrease their biosynthetic capacity and multipotency.3 Clearly, cells used for tissue engineering need to be biosynthetically active. Mauck and coworkers reported that when bovine chondrocytes and bone-marrow derived MSCs from the same animals were cultured under identical conditions chondrocytes not only created a significantly more functional tissue than MSCs they also maintained the improvement in biosynthetic and mechanical properties after 10 weeks of culture, by which time the MSCs had already reached a plateau.4 Therefore, optimizing the methods for MSC isolation, expansion, and differentiation remain critical for their effective use in tissue engineering and regenerative medicine.