Beyond Tissue Origin: Rethinking Experimental Model Selection in Rotator Cuff Research.

Rotator cuff tears are among the most common tendon disorders and a major cause of shoulder pain and functional impairment. Increasing evidence indicates that rotator cuff pathology is a complex biological disease involving inflammation, oxidative stress, hypoxia, apoptosis, cellular senescence, and dysregulated extracellular matrix (ECM) remodeling. Consequently, in vitro studies using rotator cuff-derived cells have become important tools for investigating disease mechanisms and therapeutic targets. Although rotator cuff-derived cells are widely used and generally regarded as physiologically relevant experimental models, their use is limited by restricted tissue availability, inter-donor variability, and the predominance of specimens obtained from torn or degenerative tendons. Commercially available tenocytes offer advantages in accessibility, standardization, reproducibility, and scalability, yet their use in rotator cuff research remains limited because they are not derived from rotator cuff tissue. This Opinion article provides a multifaceted and balanced reappraisal of the view that rotator cuff-derived cells are indispensable for rotator cuff research and explores the potential role of commercially available tenocytes as complementary experimental models. Current cell-based models are discussed in light of the absence of established rotator cuff-specific molecular markers and the growing recognition of tendon cell heterogeneity. This article does not advocate replacing rotator cuff-derived cells. Rather, it proposes that commercially available tenocytes may serve as complementary experimental models for investigating biological processes-including inflammation, oxidative stress, ECM metabolism, and preliminary drug screening-for which tissue-specific biology may not always be required. A stepwise strategy involving screening in commercial tenocytes, validation in rotator cuff-derived cells, and confirmation in tissue, animal, or clinical studies is proposed to balance experimental accessibility with biological relevance. Such an approach may broaden research accessibility while facilitating translational research in rotator cuff disease.