Stem and progenitor cells in the synovial joint as targets for regenerative therapy

Damage to articular cartilage, tendons, ligaments and entheses as a result of trauma, degeneration or inflammation in rheumatic diseases is prevalent. Regenerative medicine offers promising strategies for repairing damaged tissues, with the aim of restoring both their structure and function. While these strategies have traditionally relied on tissue engineering approaches using exogenous cells, interventions based on the activation of endogenous repair mechanisms are an attractive alternative. Key to advancing such approaches is a comprehensive understanding of the diversity of the stem and progenitor cells that reside in the adult synovial joint and how they function to repair damaged tissues. Advances in developmental biology have provided a lens through which to understand the origins, identities and functions of these cells, and insights into the roles of stem and progenitor cells in joint tissue repair, as well as their complex relationship with fibroblasts, have emerged. Integration of knowledge obtained through studies using advanced single-cell technologies will be crucial to establishing unified models of cell populations, lineage hierarchies and their molecular regulation. Ultimately, a more complete understanding of how cells repair tissues in adult life will guide the development of innovative pro-regenerative drugs, which are poised to enter clinical practice in musculoskeletal medicine. Stem and progenitor cells that contribute to tissue repair reside within various niches in the synovial joints of adult mammals. Understanding of the origins, identities and functions of these cells will guide the development of pro-regenerative therapeutic strategies.