Uncertainty and Sensitivity Analysis of Hair Growth Duration in Human Scalp Follicles Under Normal and Alopecic Conditions.

Abstract

Hair follicles, the organs that produce hair, go through a constant cycle composed of phases of growth, regression, and rest. During this cycle, matrix keratinocytes (MKs), the cells responsible for hair fiber synthesis, proliferate for several years and then undergo spontaneous apoptosis. Damage to MKs and perturbations in their normal dynamics result in a shortened growth phase of the hair cycle, leading to hair loss. The most common factors causing such disruption are hormonal imbalance and attacks by the immune system. Androgenetic alopecia (AGA) is a form of hair loss caused by high sensitivity to androgens, and alopecia areata (AA) is a condition where hair loss is caused by an autoimmune reaction against MKs. In this study, we inform a mathematical model for the human hair cycle with experimental data for the lengths of hair cycle phases available from male control subjects and subjects with AGA. We also connect a mathematical model for AA with estimates for the duration of hair cycle phases obtained from the literature. Subsequently, with each model we perform parameter screening, uncertainty quantification, and global sensitivity analysis, and we compare the results across control, AGA, and AA conditions. The findings reveal that, in AGA subjects, there is greater uncertainty associated with the duration of hair growth than in control subjects. Additionally, compared to control and AGA conditions, in AA it is more certain that longer hair growth phase could not be expected. The global sensitivity analysis results show that, in AGA conditions, synthesis of regulatory molecules in the dermal papilla and stem cell input to the MK population have high impact on hair growth duration, which agrees with physiological understanding for the effect of androgens on hair follicles in AGA.