Towards developing an organotypic model for the preclinical study and manipulation of human hair matrix-dermal papilla interactions

Organ culture of microdissected scalp hair follicles (HFs) has become the gold standard for human ex vivo hair research; however, availability is becoming very limited. Although various simplistic “HF-equivalent” in vitro models have been developed to overcome this limitation, they often fail to sufficiently mimic the complex cell–cell and cell–matrix interactions between epithelial and mesenchymal cell populations that underlie the specific growth processes occurring in a native HF. Here, we have attempted to overcome these limitations by developing a novel human hair research model that combines dermal papilla (DP) fibroblasts, cultured as 3-dimensional (3D) spheroids (DPS), with plucked anagen hair shafts (HS). We show that DPS express HF inductivity markers, such as alkaline phosphatase (ALP), versican and noggin, while plucked HSs retain substantial remnants of the anagen hair matrix. When cultured together, DPS adhere to and surround the plucked HS (HS-DPS), and significantly enhance HS expression of the differentiation marker keratin-85 (K85; p < 0.0001), while simultaneously decreasing the percentage of TUNEL + cells in the proximal HS (p = 0.0508). This simple model may offer a physiologically relevant first step toward evaluating HF differentiation in the human anagen hair matrix.