We can add functional mouse hair follicles to body parts that scientists have successfully grown in the lab, outside the body. Using cells obtained from embryonic mice, for the first time researchers were able to produce hair follicle organoids – small, simple versions of an organ – that grew hair. Moreover, they were able to influence the pigmentation of the hair; and, when the follicles were transplanted into living hairless mice, they continued to function across multiple hair growth cycles. This research, the team says, could help aid efforts to treat hair loss, as well as provide alternative models to animal testing and drug screening. Hair follicles form during the development of an embryo. The outer skin layer, or epidermis, and connective tissue layer next to it, the mesenchyme, mutually interact to trigger the morphogenesis process in which cells start coming together to form the organ. These epidermal-mesenchymal interactions that result in follicles are not very well understood. In a lab setting, scientists have managed to grow skin organoids, both mouse and human, that contain follicles, but successfully growing follicles in isolation has proven elusive. But organoid science has been growing more sophisticated in recent years, so a team of scientists led by biomedical engineer Tatsuto Kageyama of Yokohama National University in Japan decided to take a crack at it. They started with two types of cells harvested from embryonic mice: epithelial (skin); and mesenchymal. Some of these groups of cells were cultured with a substance called Matrigel, a mouse-derived membrane preparation that helps cells form structures; some were cultured without Matrigel. The difference was striking. The two types of cells aggregated, then spontaneously separated within the aggregate, forming an organized structure. Without the Matrigel, or when the Matrigel was added later, these structures were dumbbell-shaped, and failed to develop into functional follicles. However, when the Matrigel was added within six hours of seeding the culture with the cells, the structures consisted of a core of epithelial cells surrounded by a shell of mesenchymal cells. This arrangement, the researchers say, increases the contact area between the two cell types, facilitating the development of the blob into a follicle. Indeed, this is precisely what they observed. The core-shell blobs developed into mature, hair-producing follicle organoids with almost a 100 percent success rate, growing 2 millimeters of hair after 23 days. During this process, the researchers were able to study how the follicle developed and produced hair on the molecular level. They also tested a drug that stimulates the production of melanocytes, the cells involved in pigmentation. When this drug was added to the culture, the hairs that grew from the follicle organoids were more pigmented than hairs to which the drug had not been added. Finally, they transplanted their cultured follicles into nude mice – lab mice specifically bred with a suppressed immune system – to observe if the organoids could integrate into a living body. Once transplanted, the organoids matured into full follicles, and produced hair for several growth cycles, lasting at least 10 months. Obviously this is a mouse study, and can't be extrapolated to humans quite just yet, but human research is next on the agenda. Unlike with the mouse study, the team won't be using cells harvested from embryos, but will take cells donated by adults and reverse engineer them into stem cells, from which they hope to grow the epithelial and mesenchymal cells required. This process could be revealing in and of itself, but the end goal is an ambitious one. The team hopes that their research will lead to treatments for conditions such as alopecia or pattern baldness, which affect all genders. In addition, an in vitro model of hair follicle morphogenesis and development may reduce our reliance on animal testing. Source
