A team of researchers from the University of Southern California in Los Angeles have managed to grow hair starting from stem cells, uncovering key molecular events involved in hair growth and stimulating it in adult mice.
The new research – which has been published in the journal Proceedings of the National Academy of Sciences – offers a step-by-step explanation of the process by which hair grows. The findings pave the way for hair growth stimulation in patients with alopecia or male pattern baldness.
A team of researchers set out to examine how follicles grow out of the skin and how they produce hair by using so-called organoids, which are clusters of stem cells grown in vitro that can self-organize into an organ-like structure.
They used the 3-D structure of organoids to gain a better understanding of a certain organ, as they have similar properties to the organ it imitates – which, in this case, is the human skin.
The study’s first author is Mingxing Lei, a postdoctoral researcher in the University of Southern California’s (USC) Stem Cell laboratory.
Lei and team used skin organoids derived from both newborn and adult skin cells. Specifically, they used progenitor cells, which are a type of cell that is more differentiated than stem cells. They dissociated these from newborn and adult skin and then transplanted them into nude mice.
The researchers then took detailed time-lapse images of the 3-D cultures to see how the cells behave and how hair development occurs.
Lei and colleagues were able to see that the newborn cells formed skin-like organoids in a six-step process that started with the dissociated progenitor cells (step one), which soon aggregated (step two).
These aggregated cells then turned into polarized cysts (step three), which then transformed into so-called coalesced cysts (step four), which went on to form planar skin (step five).
In the final step of the process, the skin formed follicles (step six), which were transplanted into a mouse. Here, they produced hair.
By contrast, the researchers found, dissociated progenitor skin cells from an adult mouse neither moved past the aggregation stage nor produced any hair.
Lei and colleagues went on to study the molecular and biophysical events that underpinned this six-step hair growth process, explaining that the researchers “used a combination of bioinformatics and molecular screenings” to unravel these mechanisms.
They found increased activity in various genes, including those involved in the production of collagen – the fibrous protein that can be found in the skin and other connective tissues – and insulin, which is the hormone that regulates the levels of sugar in our bloodstream.
By inhibiting the activity of certain genes at different stages in the development of the organoid, the scientists were able to elucidate their role in transitioning from one phase to the next.
“Our investigation elucidates a relay of molecular events and biophysical processes at the core of the self-organization process during tissue morphogenesis,” write the authors. “Molecules key to the multistage morphological transition are identified and can be added or inhibited to restore the stalled process in adult cells.”
In fact, Lei and colleagues applied this newly acquired molecular and genetic knowledge to organoids created from adult skin cells, in an attempt to jump-start the hair growth process.
Significantly, Lei and team could successfully stimulate hair growth in these organoids. Adult organoids managed to produce 40 percent as much hair as the organoids derived from newborns.
“Normally, many aging individuals do not grow hair well, because adult cells gradually lose their regenerative ability,” explains senior author Prof. Cheng-Ming Chuong, of USC’s Keck School of Medicine. However, he explains that his team’s findings have implications that could change this.
“With our new findings, we are able to make adult mouse cells produce hair again. In the future, this work can inspire a strategy for stimulating hair growth in patients with conditions ranging from alopecia to baldness.”
Prof. Cheng-Ming Chuong