TY - JOUR
T1 - Development of a standardized histopathology scoring system for intervertebral disc degeneration in rat models
T2 - An initiative of the ORS spine section
AU - Lai, Alon
AU - Gansau, Jennifer
AU - Gullbrand, Sarah E.
AU - Crowley, James
AU - Cunha, Carla
AU - Dudli, Stefan
AU - Engiles, Julie B.
AU - Fusellier, Marion
AU - Goncalves, Raquel M.
AU - Nakashima, Daisuke
AU - Okewunmi, Jeffrey
AU - Pelletier, Matthew
AU - Presciutti, Steven M.
AU - Schol, Jordy
AU - Takeoka, Yoshiki
AU - Yang, Sidong
AU - Yurube, Takashi
AU - Zhang, Yejia
AU - Iatridis, James C.
N1 - Funding Information:
We gratefully acknowledge survey respondents, JOR Spine and ORS Spine section for motivating this histopathology series and for assistance in distributing surveys. Research reported in this publication was supported by funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R01AR057397. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
We gratefully acknowledge survey respondents, JOR Spine and ORS Spine section for motivating this histopathology series and for assistance in distributing surveys. Research reported in this publication was supported by funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R01AR057397. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2021 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - histology
KW - histology grading scale
KW - histopathology
KW - intervertebral disc degeneration
KW - intervertebral disc regeneration
KW - rat model
UR - http://www.scopus.com/inward/record.url?scp=85106410930&partnerID=8YFLogxK
U2 - 10.1002/jsp2.1150
DO - 10.1002/jsp2.1150
M3 - Article
AN - SCOPUS:85106410930
SN - 2572-1143
VL - 4
JO - JOR Spine
JF - JOR Spine
IS - 2
M1 - e1150
ER -