Epidermal homeostasis and radiation responses in a multiscale tissue modeling framework

Area of Science:

• Computational biology
• Dermatology
• Radiation oncology

Background:

• The skin's epidermis relies on stem cells for continuous renewal.
• High-dose radiation can damage these cells, leading to cutaneous radiation syndrome.
• Understanding skin's response to radiation is crucial for effective treatment and mitigation.

Purpose of the Study:

• To develop a multiscale computational model of skin epidermal dynamics.
• To simulate and understand the effects of ionizing radiation on skin.
• To link subcellular, cellular, and tissue-level phenomena in skin radiation response.

Main Methods:

• A multiscale computational model integrating subcellular, cellular, and tissue levels was developed.
• The model incorporated experimentally measured histological and cell kinetic parameters from swine epidermis.
• Wnt signaling-controlled cell-cycle models were applied at the subcellular level.

Main Results:

• The model successfully simulated experimental data for swine epidermis radiation response.
• Population kinetics and proliferation indices matched observations in irradiated and unirradiated swine.
• Analysis of Wnt signaling components provided insights into subcellular mechanisms.

Conclusions:

• The multiscale model provides a robust framework for studying skin epidermal dynamics under radiation.
• The integrated approach enhances understanding of ionizing radiation's pathophysiological effects on skin.
• The model aids in validating biological rules at cellular and subcellular levels.