Regulation of mesenchymal stem cell differentiation

Abstract

A population of multipotent stromal cells exists within bone marrow and other adult tissues, which is able to differentiate into different skeletal tissues such as bone, cartilage and fat. These cells are frequently referred to as mesenchymal stem cells (MSCs) and offer significant therapeutic potential, particularly in orthopaedic applications, but may also have broader roles in regenerative medicine, cancer treatment, as anti-inflammatories, immunosuppressives and vehicles for gene/protein therapy. Much attention has focused on understanding MSC biology and the regulation of differentiation to help realise these clinical aspirations. Here we review some of the key molecular determinants of MSC function, with an emphasis on transcription factor control and the cell-cell signalling pathways that regulate MSC differentiation. The source information comes from a range of different models, including isolated human MSC cultures, animal-derived MSC-like cell lines, animal models and skeletal developmental processes to provide a wide-angled overview of the important players in MSC biology and tri-lineage specification.