A 3D computational model of cervical epithelial tissue used to explore how cell characteristics and mutations affect homeostasis and tissue composition

Synopsis

Cervical cancer is the fourth most common cancer among women. Early diagnosis of precancerous lesions in the cervix is important to prevent development of invasive cervical cancer. At the same time misdiagnosis can result in unnecessary surgery. Computational simulations open up a new approach to study how cell mutations disrupt the steady state of a healthy epithelial tissue and what mutations can lead to development of preneoplastic lesions. I modified a previously used 3D individual cell-based model to simulate a dynamic healthy stratified cervical epithelium and tested it by comparing my result with diagnostic data from healthy cervical biopsies. I explored how changes in several cell characteristics modified and affected the steady state, to better understand the impact. In addition, I did simulations where a mutated stem cell was introduced into a healthy steady epithelium, to study its effect on tissue homeostasis and how uncontrolled division of mutated cells leads to a cervical intraepithelial neoplasia 3 (CIN3) pre-neoplastic lesion. My simulation results showed good resemblance to biopsy data given to us by BC cancer research center. These results yield insight into how different cell characteristics contribute to regulating tissue structure and how different kinds of cell mutations can lead to cervical pre-neoplastic lesions with different degrees of severity. This understanding can help in diagnosing cervical biopsies and possibly predict the potential severity of the lesion.