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Hairy human skin generated from stem cells

Hair-bearing human skin 49 days after being grafted to a mouse. Koehler lab, Nature

Skin is the body’s largest organ and plays a vital role in health. It helps regulate body temperature, retain body fluid, and defend against the outside world. It also allows the sensation of touch and pain.

Skin is a complex structure made up of multiple layers. It contains fat, nerves, glands, and hair follicles. Scientists have been able to grow human skin outside the body for over 40 years. However, skin grown in cultures lacked embedded structures, like hair follicles and sweat glands, found in real skin. 

A team of researchers led by Dr. Karl Koehler of Boston Children’s Hospital aimed to create complex, hair-bearing skin in the lab using human pluripotent stem cells, which are present early in embryonic development and have the potential to transform into any cell type in the body.

The study was funded in part by NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute on Deafness and other Communication Disorders (NIDCD), and National Institute of Child Health and Human Development (NICHD). Findings were published in Nature on June 3, 2020.

The scientists had successfully generated hair-bearing skin from mouse stem cells in the past. To transform human stem cells, they started by revisiting a culture method that Koehler had used in earlier work to create sound-sensing cells in the inner ear. The researchers applied a combination of growth factors and small molecules to coax the stem cells into skin tissue.

After 4-5 months, the stem cells had grown into a small, cyst-like "organoid" that replicated the micro-anatomy of skin. This “skin in a dish” had both the top and bottom layers of skin (epidermis and dermis), fat, nerves, and was able to sprout hair. Hair buds, which produce hair, formed after about 70 days, similar to the timing during embryonic development. The organoids also produced specialized cell types like Merkel cells, which are responsive to touch.

The team analyzed the organoid and determined that it was similar to the facial skin of a fetus in the second trimester.

The researchers next grafted the hair-bearing skin onto the backs of nude mice. Within a month, the mice grew small, pigmented hairs at the site of the graft. The transplanted skin had many features unique to adult human skin, including sebaceous glands which secrete lubricating oil for the skin and hair.

Being able to create hair-bearing skin in the lab may help advance research into skin development and diseases. It could have implications for treating baldness as well, although many challenges remain.

“We now have a technique that could generate nearly unlimited hair follicles for transplantation,” Koehler says. “But immune rejection is a major hurdle, and generating follicles tailored to an individual will be incredibly costly and take a year or more.”

—by Erin Bryant