Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Development of an Ex Vivo Functional Assay for Prediction of Irradiation Related Toxicity in Healthy Oral Mucosa Tissue

Katrin S. Pachler
,
Iris Lauwers
,
Nicole S. Verkaik
,
Marta Rovituso
ORCID logo ,
Ernst van der Wal
,
Hetty Mast
,
Brend P. Jonker
ORCID logo ,
Aniel Sewnaik
,
Jose A. Hardillo
ORCID logo ,
Stijn Keereweer
ORCID logo ,
Dominiek Monserez
ORCID logo ,
Bernd Kremer
,
Sjors Koppes
,
Thierry P.P. van den Bosch
ORCID logo ,
Gerda M. Verduijn
ORCID logo ,
Steven Petit
ORCID logo ,
Brita S. Sørensen
ORCID logo ,
Dik C. van Gent
ORCID logo ,
Marta E. Capala
*
Version 1 : Received: 14 May 2024 / Approved: 15 May 2024 / Online: 15 May 2024 (07:28:30 CEST)

A peer-reviewed article of this Preprint also exists.

Pachler, K.S.; Lauwers, I.; Verkaik, N.S.; Rovituso, M.; van der Wal, E.; Mast, H.; Jonker, B.P.; Sewnaik, A.; Hardillo, J.A.; Keereweer, S.; Monserez, D.; Kremer, B.; Koppes, S.; van den Bosch, T.P.P.; Verduijn, G.M.; Petit, S.; Sørensen, B.S.; van Gent, D.C.; Capala, M.E. Development of an Ex Vivo Functional Assay for Prediction of Irradiation Related Toxicity in Healthy Oral Mucosa Tissue. Int. J. Mol. Sci. 2024, 25, 7157. Pachler, K.S.; Lauwers, I.; Verkaik, N.S.; Rovituso, M.; van der Wal, E.; Mast, H.; Jonker, B.P.; Sewnaik, A.; Hardillo, J.A.; Keereweer, S.; Monserez, D.; Kremer, B.; Koppes, S.; van den Bosch, T.P.P.; Verduijn, G.M.; Petit, S.; Sørensen, B.S.; van Gent, D.C.; Capala, M.E. Development of an Ex Vivo Functional Assay for Prediction of Irradiation Related Toxicity in Healthy Oral Mucosa Tissue. Int. J. Mol. Sci. 2024, 25, 7157.

Abstract

Background: Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delay leading to worse outcomes and decreased quality of life. Therefore, there is an urgent need for an approach to predict normal mucosa response in patients prior to treatment. Methods: We here describe an assay to detect irradiation response in patient healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated, and cultured for three days. Seven samples were irradiated with X-ray and three additional samples were irradiated with both X-ray and protons. Results: Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample, using standardized automated image analysis. Furthermore, increased levels of inflammation inducing factors - major drivers in mucositis development - could be detected after irradiation. Conclusion: This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

Keywords

Mucositis; oral mucosa; ex vivo; radiosensitivity prediction; personalized medicine

Subject

Biology and Life Sciences, Cell and Developmental Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.