Reporting Standards in Clinical Studies Evaluating Bone Marrow Aspirate Concentrate: A Systematic Review.

PURPOSE: To perform a systematic review of clinical studies evaluating bone marrow aspirate concentrate (BMAC) in the treatment of musculoskeletal pathology to compare levels of reporting with recently published minimum standards. METHODS: A systematic review of the clinical literature from August 2002 to August 2017 was performed. Human clinical studies published in English and involving the administration of BMAC for musculoskeletal applications were included. Studies evaluating non-concentrated preparations of bone marrow aspirate or preparations of laboratory cultured cells were excluded. Studies evaluating the treatment of dental or maxillofacial conditions were excluded. Similarly, in vitro studies, editorials, letters to the editor, and reviews were excluded. Levels of reporting were compared with previously published minimum standards agreed on through an international Delphi consensus process. RESULTS: Of 1,580 studies identified on the initial search, 46 satisfied the criteria for inclusion. Considerable deficiencies in reporting of key variables including the details of BMAC preparation and composition were noted. Studies reported information on only 42% (range, 25%-60%) of the variables included within established minimum reporting standards. No study provided adequate information to enable the precise replication of preparation protocols and accurate characterization of the BMAC formulation delivered. CONCLUSIONS: We found that all existing clinical studies in the literature evaluating BMAC for orthopaedic or sports medicine applications are limited by inadequate reporting of both preparation protocols and composition. Deficient reporting of the variables that may critically influence outcomes precludes interpretation, prevents other researchers from reproducing experimental conditions, and makes comparisons across studies difficult. We encourage the adoption of emerging minimum reporting standards for clinical studies evaluating the use of mesenchymal stem cells in orthopaedics. LEVEL OF EVIDENCE: Level IV, systematic review of Level I through IV studies.

Reporting of Mesenchymal Stem Cell Preparation Protocols and Composition: A Systematic Review of the Clinical Orthopaedic Literature.

BACKGROUND: Mesenchymal stem cells (MSCs) are increasingly being used in the treatment of a wide variety of sports-related conditions. Despite this enthusiasm, the biological properties of MSCs and their effects on musculoskeletal tissue healing remain poorly understood. MSC-based strategies encompass cell populations with heterogeneous phenotypes isolated from multiple tissues and using different methods. Therefore, comprehensive reporting of the source, preparation methods, and characteristics of MSC strategies is essential to enable interpretation of results. PURPOSE: To perform a systematic review of levels of reporting of key variables in MSC preparation and composition for clinical studies evaluating MSC-based therapies in the treatment of musculoskeletal conditions. STUDY DESIGN: Systematic review. METHODS: A systematic review of the clinical orthopaedic and sports medicine literature from 2002 to 2017 was performed. The following inclusion criteria were used: human clinical trials, published in the English language, involving the administration of MSC-based therapies for orthopaedic or sports medicine applications. In vitro or ex vivo studies, editorials, letters to the editor, and studies relating to cosmetic, neurological, or dental applications were excluded. RESULTS: Of the 1259 studies identified on the initial search, 36 studies were found to satisfy the inclusion criteria for analysis on comprehensive review. Fifty-seven percent of studies evaluated bone marrow-derived MSCs, 41% evaluated adipose-derived MSCs, and 2% evaluated synovium-derived MSCs. Considerable deficiencies in the reporting of key variables, including the details of stem cell processing, culture conditions, and the characteristics of cell populations delivered, were noted. Overall, studies reported only 52% (range, 30%-80%) of variables that may critically influence outcome. No study provided adequate information relating to all of these variables. CONCLUSION: All existing clinical studies evaluating MSCs for orthopaedic or sports medicine applications are limited by inadequate reporting of both preparation protocols and composition. Deficient reporting of the variables that may critically influence outcome precludes interpretation, prevents others from reproducing experimental conditions, and makes comparisons across studies difficult. We encourage the adoption of emerging minimum reporting standards for clinical studies evaluating the use of MSCs in orthopaedics.