The Role of Mesenchymal Stem Cells

©2006 British Editorial Society of Bone and Joint Surgery doi:10.1302/0301-620X.88B4. 17060 $2.00 J Bone Joint Surg [Br] 2006; 88-B:421-6. The management of large bony defects and cartilage loss continues to be a challenge to trauma and orthopaedic surgeons. The treatment of these conditions has evolved over the years and has comprised of many techniques, such as autologous bone grafting, distraction osteogenesis and free fibular vascularised bone grafting. Advances in tissue engineering and regeneration have led to the development of new techniques and therapeutic options, while the introduction of pluripotent mesenchymal stem cells (MSCs) into the clinical setting opens new horizons. Autologous or allogenic MSCs can be expanded in monolayers and may then be loaded into a variety of scaffolds before implantation into a patient. This technique leads to regeneration of bone and cartilage by local induction of osteogenesis and chondrogenesis. This review article focuses on the latest advances in bone and cartilage regeneration using MSCs. The issues of ‘growing’ bone and restoring cartilage have been debated for centuries. In the past, extensive bone loss, as might occur in a large diaphyseal defect of a long bone, was thought to be incurable, with amputation often inevitable. In the early 19th century, the concept of autologous bone grafting was introduced, although it only proved successful for small defects.1 In the mid-1950s, Ilizarov introduced a revolutionary method for salvaging limbs with severe bone loss. He used distraction osteogenesis, a technique which is still popular today.2,3 Subsequently, in the mid-1970s, the concept of free fibular vascularised bone grafting was introduced, thereby providing another dimension to the treatment of injuries associated with extensive bone loss.4 Also at this time the repair of joint cartilage defects was revolutionised,5 with the introduction of cartilage resurfacing perhaps becoming an alternative to joint replacement. While good results have been reported and these techniques have allowed many patients to retain their limbs, research into the development of more effective treatments has continued. Advances in all areas of medicine, including molecular medicine, molecular biology, tissue engineering and genetics have opened new horizons in both the philosophy and capability of growing tissue, in particular that of bone and cartilage. The discovery by Urist6 of bone morphogenetic protein (BMP) as well as a better understanding of the biological processes which govern the healing and repair of tissues, has led to the development of new strategies for the regeneration of tissues. In addition, the ability to isolate and culture MSCs has encouraged reexamination of the treatment of many musculoskeletal conditions.