Patient-Derived Organotypic Epithelial Rafts Model Phenotypes in Juvenile-Onset Recurrent Respiratory Papillomatosis
| Autor: | Kathryn A. Wikenheiser-Brokamp, Matthew Kofron, El Mustapha Bahassi, Denis Lee, Adam Lane, Susanne I. Wells, Paul F. Lambert, Sonya Ruiz-Torres, Alessandro de Alarcon, Hannah Lodin, Mary C. Bedard, Adrean Carlile, Najim Ameziane, Marion G. Brusadelli, David F. Smith |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell lcsh:QR1-502 Alphapapillomavirus Biology Real-Time Polymerase Chain Reaction Article lcsh:Microbiology 03 medical and health sciences Basal (phylogenetics) Organ Culture Techniques 0302 clinical medicine Risk Factors Virology JoRRP medicine Humans 030223 otorhinolaryngology Respiratory Tract Infections Confluency low-risk HPV 3D organotypic rafts business.industry Papillomavirus Infections Epithelial Cells medicine.disease Phenotype 030104 developmental biology Infectious Diseases Juvenile onset medicine.anatomical_structure Cancer research RNA Viral Papilloma Personalized medicine Recurrent Respiratory Papillomatosis business |
| Zdroj: | Viruses, Vol 13, Iss 68, p 68 (2021) Viruses Volume 13 Issue 1 |
| ISSN: | 1999-4915 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|