Patient-Derived Organotypic Epithelial Rafts Model Phenotypes in Juvenile-Onset Recurrent Respiratory Papillomatosis
Open Access
- 6 January 2021
- Vol. 13 (1), 68
- https://doi.org/10.3390/v13010068
Abstract
Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is driven by human papillomavirus (HPV) low-risk strains and is associated with significant morbidity. While previous studies of 2D cultures have shed light on disease pathogenesis and demonstrated the utility of personalized medicine approaches, monolayer cultures lack the 3D tissue architecture and physiology of stratified, sequentially differentiated mucosal epithelium important in RRP disease pathogenesis. Herein we describe the establishment of JoRRP-derived primary cell populations that retain HPV genomes and viral gene expression in culture. These were directly compared to cells from matched adjacent non-diseased tissue, given the known RRP patient-to-patient variability. JoRRP papilloma versus control cells displayed decreased growth at subconfluency, with a switch to increased growth after reaching confluency, suggesting relative resistance to cell-cell contact and/or differentiation. The same papilloma cells grown as 3D organotypic rafts harbored hyperproliferation as compared to controls, with increased numbers of proliferating basal cells and inappropriately replicating suprabasal cells, mimicking phenotypes in the patient biopsies from which they were derived. These complementary model systems provide novel opportunities to elucidate disease mechanisms at distinct stages in JoRRP progression and to identify diagnostic, prognostic and therapeutic factors to personalize patient management and treatment.Keywords
Funding Information
- National Institute of Allergy and Infectious Diseases (R21AI142704)
- National Institute of Environmental Health Sciences (2T32ES007250)
- National Cancer Institute (5P01CA022443, 1R35CA210807)
This publication has 30 references indexed in Scilit:
- Conditionally reprogrammed cells represent a stem-like state of adult epithelial cellsProceedings of the National Academy of Sciences of the United States of America, 2012
- The Papillomavirus Episteme: a central resource for papillomavirus sequence data and analysisNucleic Acids Research, 2012
- Use of Reprogrammed Cells to Identify Therapy for Respiratory PapillomatosisThe New England Journal of Medicine, 2012
- Recurrent Respiratory PapillomatosisOtolaryngologic Clinics of North America, 2012
- Primer-BLAST: A tool to design target-specific primers for polymerase chain reactionBMC Bioinformatics, 2012
- ROCK Inhibitor and Feeder Cells Induce the Conditional Reprogramming of Epithelial CellsThe American Journal of Pathology, 2012
- Recurrent Respiratory Papillomatosis: A ReviewThe Laryngoscope, 2008
- Recurrent respiratory papillomatosisArchives of Disease in Childhood, 2006
- Condyloma in pregnancy is strongly predictive of Juvenile-Onset recurrent respiratory papillomatosisObstetrics & Gynecology, 2003
- Biosynthesis of Human Papillomavirus from a Continuous Cell Line Upon Epithelial DifferentiationScience, 1992