Caterson EJ, Nesti LJ, Albert T, Danielson K and Tuan R (2001). Application of mesenchymal stem cells in the regeneration of musculoskeletal tissues. MedGenMed. E1. Summary: Mesenchymal stem cells are a rare population of undifferentiated cells, isolated from adult tissue sources, that have the capacity to differentiate into mesodermal lineages, including bone, fat, muscle, cartilage, tendon, and marrow stroma. These cell populations may be expanded in culture and subsequently permitted to differentiate into the desired lineage. This directed differentiation may be reached by the application of bioactive molecules, specific growth factors, and signaling molecules. Understanding the functional potential of these cells and the signaling mechanisms underlying their differentiation should lead to innovative protocols for clinical orthopaedic interventions. Clinically applicable techniques to isolate, expand, and reimplant these autogenous cells will become part of the repertoire of orthopaedic therapy. In the presence of extrinsic signaling molecules, provided by both the clinician and the local cellular environment, the intrinsic multipotential nature of the stem cells may be realized for applications such as the replacement of bone graft for segmental defects, nonunions, and spinal fusions. Additional applications may include treatment of full-thickness articular defects and articular resurfacing by site-specific delivery of stem cells. The ultimate goal is directed cellular regeneration of damaged or diseased musculoskeletal tissue. Currently, the limitation is our knowledge and ability to direct this differentiation, but with further study molecular orthopaedic interventions should become a reality. < st_uids=11320340> Department of Orthopaedic Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA.