Poor consideration of tissue loading in randomised trials of MSC interventions for tendon pathology: A systematic review using the TIDieR framework.

Purpose: Mesenchymal Stem Cell (MSC) interventions are a new frontier in the clinical management of tendon injury. In terms of tissue repair and regeneration, both tendon cells and stem cells are mechanotransductive, i.e. they require mechanical stimulus, it therefore follows that well-structured post-intervention rehabilitation is needed to support MSC interventions and should be well considered in MSC clinical trials. This review evaluates the completeness of reporting of rehabilitation following MSC interventions for tendon pathology in clinical trials. Methods: A systematic review of randomised controlled trials was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and using the Template for Intervention Description and Replication (TIDieR) framework. We applied a PICO framework to inform our search strategy to find clinical trials that used either bone marrow or adipose-derived MSCs as an intervention on human tendons. Electronic searches were conducted in Medline, PubMed, CINAHL and SPORTDiscus, from inception to May 2024. MeSH terms and Boolean operators were employed, with English language the only filter. Data was extracted to complete the TIDieR checklist separately by three researchers and cross checked by a third to ensure consistency. The Cochrane risk of bias tool 2 was employed to review trial internal validity. Results: The search returned 142 articles. Following removal of duplicates, 118 papers were evaluated against the inclusion criteria. Eight RCTs were included, comprising five in rotator cuff pathology and individual trials in Achilles, gluteal and patellar tendinopathies. Various MSC preparations were utilised and reported, however the accompanying rehabilitation framework was poorly described with a mean TIDieR score of 2.38 ± 2.56 points (of a maximum of 12). The maximum score was 6/12 for a single trial, while 3 scored 0/12. There was large variability in rehabilitation reporting, however 'why', and 'where' domains were reported in only 1 study, with 'tailoring', 'modifications', 'adherence' and 'fidelity' TIDieR domains not reported in any trial. The included studies demonstrate a high risk of bias. Concerns regarding participant randomisation, participant blinding and group allocation were common across the included studies. Conclusion: Current randomised controlled trials demonstrate a poor standard of reporting of physical rehabilitation following MSC interventions for tendon pathologies, and highlight the lack of consideration given to post intervention loading. More comprehensive trials that fully incorporate post-MSC loading parameters are required to better understand MSC efficacy in tendon repair. Level of Evidence: Level II, therapeutic studies.