Development of a standardized histopathology scoring system for intervertebral disc degeneration in rat models: An initiative of the ORS spine section.

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

Journal

JOR spine
ISSN: 2572-1143
Titre abrégé: JOR Spine
Pays: United States
ID NLM: 101722350

Informations de publication

Date de publication:
Jun 2021
Historique:
received: 30 11 2020
revised: 09 04 2021
accepted: 18 04 2021
entrez: 2 8 2021
pubmed: 3 8 2021
medline: 3 8 2021
Statut: epublish

Résumé

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. This study aimed to develop a histology grading system to quantify IVD degeneration for different rat models. 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. 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. 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.

Sections du résumé

BACKGROUND 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 OBJECTIVE
This study aimed to develop a histology grading system to quantify IVD degeneration for different rat models.
MATERIALS & METHODS 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 34337335
doi: 10.1002/jsp2.1150
pii: JSP21150
pmc: PMC8313153
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e1150

Subventions

Organisme : NIAMS NIH HHS
ID : R01 AR078857
Pays : United States

Informations de copyright

© 2021 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.

Déclaration de conflit d'intérêts

The authors declare no conflicts of interest.

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Auteurs

Alon Lai (A)

Leni and Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New York USA.

Jennifer Gansau (J)

Leni and Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New York USA.

Sarah E Gullbrand (SE)

McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA.

James Crowley (J)

Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School University of New South Wales Sydney Australia.

Carla Cunha (C)

i3S-Instituto de Investigação e InovaçãoemSaúde Universidade do Porto Porto Portugal.

Stefan Dudli (S)

University Clinic of Rheumatology, Center of Experimental Rheumatology Balgrist University Hospital, University of Zurich Zurich Switzerland.

Julie B Engiles (JB)

Department of Pathobiology, New Bolton Center, School of Veterinary Medicine University of Pennsylvania Kennett Square Pennsylvania USA.

Marion Fusellier (M)

Regenerative Medicine and Skeleton, Inserm, UMR 1229, RMeS Université de Nantes, ONIRIS Nantes Cedex France.

Raquel M Goncalves (RM)

i3S-Instituto de Investigação e InovaçãoemSaúde Universidade do Porto Porto Portugal.
Instituto de CiênciasBiomédicas Abel Salazar Universidade do Porto Porto Portugal.

Daisuke Nakashima (D)

Department of Orthopaedic Surgery Keio University School of Medicine Tokyo Japan.

Jeffrey Okewunmi (J)

Leni and Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New York USA.

Matthew Pelletier (M)

Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School University of New South Wales Sydney Australia.

Steven M Presciutti (SM)

Department of Orthopaedic Surgery Emory University Atlanta Georgia USA.

Jordy Schol (J)

Department of Orthopaedic Surgery, Surgical Science Tokai University School of Medicine Isehara Japan.

Yoshiki Takeoka (Y)

Department of Orthopaedic Surgery Brigham and Women's Hospital Boston Massachusetts USA.

Sidong Yang (S)

Department of Spinal Surgery The Third Hospital of Hebei Medical University Shijiazhuang China.

Takashi Yurube (T)

Department of Orthopaedic Surgery Kobe University Graduate School of Medicine Kobe Japan.

Yejia Zhang (Y)

McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA.

James C Iatridis (JC)

Leni and Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New York USA.

Classifications MeSH