Editorial Commentary: Cell-Based Therapies for Articular Cartilage Repair Require Precise Progenitor Cell Characterization and Determination of Mechanism of Action

Abstract

Biologics and cell-based therapies, in particular, have come to the forefront of orthopaedic sports medicine as agents with therapeutic and regenerative potential. Autologous chondrocyte implantation has been used successfully for many years, but a recent focus on autologous progenitor cells derived from bone marrow aspirate, adipose tissue, and/or synovium has garnered significant interest. Mobilized peripheral blood mononuclear cells [PBMCs or connective tissue progenitors (CTPs)] represent a promising cell population for potential use in articular cartilage repair. The term "stem cell" has become widely popularized, but more specific language identifying the cell type by donor type, tissue of origin, cell surface marker profile, culture conditions, and other cell behavior/characteristics should be used. In 2019, Murray et al. proposed a five-item "DOSES" tool in an effort to encourage standardized reporting for cell-based therapies emphasizing donor, origin of tissue, separation from other cell types/preparation method, exhibited cell characteristics associated with behavior, and site of delivery. The advantages of the DOSES tool include both simplicity and ability to be applied to cell types not yet discovered. However, a universally accepted list of criteria for biologics does not yet exist. Additional research is necessary to better elucidate the precise mechanisms by which cell therapies have a clinical effect and define whether the therapies for the treatment of cartilage pathology merely help alleviate symptoms or actually provide structural improvements. There are few data to suggest exogenous cell therapies directly engraft, so identifying the paracrine mediators produced by these cells would be an area of further interest.