Human Knee as an Organ: Joint Tissue Collection, Processing, and Scoring for Multimodal Analyses

All knee joint tissues undergo aging-associated and osteoarthritis-associated changes, but our understanding of the knee as an organ, and the tissue crosstalk in homeostasis, aging, and osteoarthritis, is limited. The emergence of molecular profiling imaging technologies now enables comprehensive profiling of joint tissues to address these knowledge gaps. Successful application of these novel technologies requires a precise clinical diagnosis and a rigorous and consistent definition of tissue-specific variables, including documentation of the regions of interest selected for macroscopic, histological, cellular, and molecular characterization. Macroscopic and histological scoring systems represent a benchmark for the interpretation of cellular and molecular analyses. Thus, standardizing these systems is essential to minimize experimental variability. Currently, most joint tissues lack a universally accepted scoring system, and various histological features are selected and quantified using different methods, limiting comparability and reproducibility across studies. Here, we review current methods, discuss limitations, and propose new approaches based on features that should be consistently evaluated across tissue types to overcome these caveats.