The Leiden ex vivo human growth plate model in severe tall stature: a proof-of-concept study

Background: Viable pediatric human growth plate (GP) tissue is rarely available for translational research, limiting direct investigation of human longitudinal bone growth and pediatric growth disorders. In this proof-of-concept study, we aimed to determine whether it is feasible to establish a clinically integrated ex vivo human GP model using tissue obtained during routine percutaneous epiphysiodesis (PE) procedures in adolescents treated for extreme tall stature or leg length difference due to trauma. Methods: GP tissue and cells were collected during PE and processed using protocols adapted from established methods of human osteoarthritic cartilage processing within the RAAK study. Feasibility was assessed by evaluating tissue collection, cell isolation, contamination rate, monolayer expansion, and generation of three-dimensional cartilage pellets. Proliferation of GP-derived chondrocytes was compared with osteoarthritis-derived articular chondrocytes, and histological assessment was performed to evaluate cartilage-like matrix formation. Results: Across consecutive surgical procedures, viable GP tissue could be obtained reproducibly, with only few samples failing to yield cells and no relevant contamination issues. Isolated GP chondrocytes expanded successfully in two-dimensional culture and showed a strong early proliferative response compared with RAAK-derived chondrocytes. In addition, GP-derived cells formed three-dimensional organoids and histology confirmed cartilage-like matrix deposition supporting their capacity to generate neo-cartilage tissue in vitro. Conclusion: This study demonstrates feasibility to obtain, culture, and functionally assess viable human GP tissue from routine PE surgery. As such, the Leiden ex vivo human GP model provides a unique platform to study local mechanisms of endochondral bone growth, link genetic determinants of height to functional GP biology, and support future therapeutic research in pediatric growth disorders.