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

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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.

Original languageEnglish
Article numbere1150
JournalJOR Spine
Volume4
Issue number2
DOIs
StatePublished - Jun 2021

Keywords

  • histology
  • histology grading scale
  • histopathology
  • intervertebral disc degeneration
  • intervertebral disc regeneration
  • rat model

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