Development of a standardized histopathology scoring system for intervertebral disc degeneration in rat models: An initiative of the ORS spine section
Alon Lai,
Jennifer Gansau,
Sarah E. Gullbrand,
James Crowley,
Carla Cunha,
Stefan Dudli,
Julie B. Engiles,
Marion Fusellier,
Raquel M. Goncalves,
Daisuke Nakashima,
Jeffrey Okewunmi,
Matthew Pelletier,
Steven M. Presciutti,
Jordy Schol,
Yoshiki Takeoka,
Sidong Yang,
Takashi Yurube,
Yejia Zhang,
James C. Iatridis
Affiliations
Alon Lai
Leni and Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New York USA
Jennifer Gansau
Leni and Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New York USA
Sarah E. Gullbrand
McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA
James Crowley
Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School University of New South Wales Sydney Australia
Carla Cunha
i3S‐Instituto de Investigação e InovaçãoemSaúde Universidade do Porto Porto Portugal
Stefan Dudli
University Clinic of Rheumatology, Center of Experimental Rheumatology Balgrist University Hospital, University of Zurich Zurich Switzerland
Julie B. Engiles
Department of Pathobiology, New Bolton Center, School of Veterinary Medicine University of Pennsylvania Kennett Square Pennsylvania USA
Marion Fusellier
Regenerative Medicine and Skeleton, Inserm, UMR 1229, RMeS Université de Nantes, ONIRIS Nantes Cedex France
Raquel M. Goncalves
i3S‐Instituto de Investigação e InovaçãoemSaúde Universidade do Porto Porto Portugal
Daisuke Nakashima
Department of Orthopaedic Surgery Keio University School of Medicine Tokyo Japan
Jeffrey Okewunmi
Leni and Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New York USA
Matthew Pelletier
Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School University of New South Wales Sydney Australia
Steven M. Presciutti
Department of Orthopaedic Surgery Emory University Atlanta Georgia USA
Jordy Schol
Department of Orthopaedic Surgery, Surgical Science Tokai University School of Medicine Isehara Japan
Yoshiki Takeoka
Department of Orthopaedic Surgery Brigham and Women's Hospital Boston Massachusetts USA
Sidong Yang
Department of Spinal Surgery The Third Hospital of Hebei Medical University Shijiazhuang China
Takashi Yurube
Department of Orthopaedic Surgery Kobe University Graduate School of Medicine Kobe Japan
Yejia Zhang
McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA
James C. Iatridis
Leni and Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New York USA
Abstract Background Rats are a widely accepted preclinical model for evaluating intervertebral disc (IVD) degeneration and regeneration. IVD morphology is commonly assessed using histology, which forms the foundation for quantifying the state of IVD degeneration. IVD degeneration severity is evaluated using different grading systems that focus on distinct degenerative features. A standard grading system would facilitate more accurate comparison across laboratories and more robust comparisons of different models and interventions. Aims This study aimed to develop a histology grading system to quantify IVD degeneration for different rat models. Materials & Methods This study involved a literature review, a survey of experts in the field, and a validation study using 25 slides that were scored by 15 graders from different international institutes to determine inter‐ and intra‐rater reliability. Results A new IVD degeneration grading system was established and it consists of eight significant degenerative features, including nucleus pulposus (NP) shape, NP area, NP cell number, NP cell morphology, annulus fibrosus (AF) lamellar organization, AF tears/fissures/disruptions, NP‐AF border appearance, as well as endplate disruptions/microfractures and osteophyte/ossification. The validation study indicated this system was easily adopted, and able to discern different severities of degenerative changes from different rat IVD degeneration models with high reproducibility for both experienced and inexperienced graders. In addition, a widely‐accepted protocol for histological preparation of rat IVD samples based on the survey findings include paraffin embedding, sagittal orientation, section thickness < 10 μm, and staining using H&E and/or SO/FG to facilitate comparison across laboratories. Conclusion The proposed histological preparation protocol and grading system provide a platform for more precise comparisons and more robust evaluation of rat IVD degeneration models and interventions across laboratories.
