Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth

Abstract

Significance Growth of de novo hair follicles in adult skin occurs by a process known as hair neogenesis. One way of initiating neogenesis is to place dermal papillae isolated from the hair follicle in contact with an overlying epidermis where they reprogram the epidermis to adopt a follicular fate. This approach, however, has not been successful using cultured human dermal papilla cells in human skin because the cells lose their ability to induce hair growth after expansion in vitro. In this paper, we demonstrate that by manipulating cell culture conditions to establish three-dimensional papilla spheroids, we restore dermal papilla inductivity. We also use several systems biology approaches to gain a comprehensive understanding of the molecular mechanisms that underlie this regenerative process.