The Leiden ex vivo human growth plate model in severe tall stature: a proof-of-concept study
- 1Dept. of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands
Abstract
Background: Viable 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 feasibility to establish a clinically integrated ex vivo human growth plate 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: Growth plate tissue and cells were collected during PE and processed using protocols adapted from established methods of human osteoarthritic cartilage collection within the RAAK study. Collected tissues and three-dimensional cartilage pellets generated from isolated cells were assessed by histology. Proliferation of GP-derived chondrocytes was compared with osteoarthritis-derived articular chondrocytes. Results: Across consecutive surgical procedures, viable GP tissue could be obtained reproducibly including the node of Ranvier, with only few samples failing to yield cells and no contamination. Isolated GP chondrocytes expanded successfully in two-dimensional culture and showed a stronger 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 growth plate tissue from routine PE surgery. As such, the Leiden ex vivo human growth plate model provides a unique platform to study local mechanisms of endochondral bone growth, link genetic determinants of height to functional growth plate biology, and support future therapeutic research in pediatric growth disorders.
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BibTeX
@misc{tuerlings2026leiden,
title = {{The Leiden ex vivo human growth plate model in severe tall stature: a proof-of-concept study}},
author = {M. Tuerlings and Y. F. M. Ramos and H. E. D. Suchiman and S. Sayedipour and S. D. Joustra and A. Rabelink-Hoogenstraaten and H. A. van Duyvenvoorde and D. R. J. Kempink and P. Bas de Witte and I. Meulenbelt and C. de Bruin},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.25.746685},
url = {https://www.biorxiv.org/content/10.64898/2026.08.25.746685v2},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - The Leiden ex vivo human growth plate model in severe tall stature: a proof-of-concept study
AU - M. Tuerlings
AU - Y. F. M. Ramos
AU - H. E. D. Suchiman
AU - S. Sayedipour
AU - S. D. Joustra
AU - A. Rabelink-Hoogenstraaten
AU - H. A. van Duyvenvoorde
AU - D. R. J. Kempink
AU - P. Bas de Witte
AU - I. Meulenbelt
AU - C. de Bruin
PY - 2026
DA - 2026/08/25
PB - bioRxiv
DO - 10.64898/2026.08.25.746685
UR - https://www.biorxiv.org/content/10.64898/2026.08.25.746685v2
AB - Background: Viable 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 feasibility to establish a clinically integrated ex vivo human growth plate 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: Growth plate tissue and cells were collected during PE and processed using protocols adapted from established methods of human osteoarthritic cartilage collection within the RAAK study. Collected tissues and three-dimensional cartilage pellets generated from isolated cells were assessed by histology. Proliferation of GP-derived chondrocytes was compared with osteoarthritis-derived articular chondrocytes. Results: Across consecutive surgical procedures, viable GP tissue could be obtained reproducibly including the node of Ranvier, with only few samples failing to yield cells and no contamination. Isolated GP chondrocytes expanded successfully in two-dimensional culture and showed a stronger 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 growth plate tissue from routine PE surgery. As such, the Leiden ex vivo human growth plate model provides a unique platform to study local mechanisms of endochondral bone growth, link genetic determinants of height to functional growth plate biology, and support future therapeutic research in pediatric growth disorders.
ER -