Patient-Derived Organotypic Epithelial Rafts Model Phenotypes in Juvenile-Onset Recurrent Respiratory Papillomatosis

Area of Science:

• Oncology
• Virology
• Cell Biology

Background:

• Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is a rare, HPV-driven disease causing significant morbidity.
• Previous 2D cell culture models lack the 3D architecture crucial for understanding RRP pathogenesis.
• Patient-to-patient variability necessitates models that reflect in vivo disease characteristics.

Purpose of the Study:

• To establish and characterize 3D organotypic raft cultures from JoRRP patient-derived cells.
• To compare the growth and differentiation patterns of JoRRP cells versus normal cells in 3D culture.
• To develop improved models for studying JoRRP progression and identifying therapeutic targets.

Main Methods:

• Primary cell cultures derived from JoRRP papilloma and matched normal tissues.
• Culture of cells in 2D monolayers and 3D organotypic rafts.
• Analysis of cell proliferation, differentiation, and HPV gene expression.

Main Results:

• JoRRP cells exhibited altered growth kinetics in 2D culture, with increased growth post-confluency.
• 3D organotypic raft cultures of JoRRP cells showed hyperproliferation and aberrant suprabasal cell replication.
• These phenotypes in 3D models closely mimicked those observed in patient biopsies.

Conclusions:

• Established 3D organotypic raft models accurately recapitulate JoRRP phenotypes.
• These models offer a platform for elucidating disease mechanisms and identifying personalized treatment strategies.
• The models can aid in discovering diagnostic, prognostic, and therapeutic factors for JoRRP management.