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Adding to the catalog of body parts that can be cultivated in Petri dishes, scientists at the Indiana University School of Medicine have created the first lab-grown hair.

Their study, published in Cell Reports, could lead to next-generation skin grafting techniques and enable development of drugs for diseases such as cancer, alopecia, and acne.

Discovery of the follicle-creating process came serendipitously, during the team’s previous experiment to generate inner ear cells from embryonic mouse stem cells (mESCs). To begin, specific signaling molecules were introduced to a spherical cluster of mESCs. These chemical cues induced the cells to transform into a new type, which are the precursors of epidermis tissue, the outermost layer of the skin. Unexpectedly, the culture then differentiated further.

“In the developing embryo, the inner ear comes from the same layer of cells as the top layer of the skin [the epidermis], so it was no surprise that skin and inner ear tissue formed in tandem,” said lead researcher Karl Koehler in a statement. “We were surprised to find that the bottom layer of the skin, the dermis, also develops.”

The epidermis is a simple layer of flattened cells that provide a barrier between the body and the outside environment. The dermis is a highly varied composite of connective tissue interspersed with numerous structures, including nerves, sweat and sebaceous glands, and blood vessels.

In the study, Koehler’s team played around with different culture conditions until hitting upon an environment that caused their dual-layered cluster to self-organize into a miniature model of skin, called an organoid. They observed as the organoid underwent the same key steps of natural skin development that occur in utero, including, to their amazement, the spontaneous sprouting of hair follicles.

The hair follicles (red) grow radially out of spherical skin organoids and contain follicle-initiating dermal papilla cells (green cells) and hair shafts (cyan). Artwork by Jiyoon Lee and Karl R. Koehler.

“In addition to the major epidermal and dermal cell types we also found specialized cell types, such as melanocytes [pigment cells], Merkel cells [touch sensing cells], adipocytes [fat cells], sebaceous gland cells, and hair follicle stem cells in organoids,” Dr Koehler said.

“This is fascinating because it shows that if we derive the basic building blocks of skin together in culture, then these diverse cell types will self-assemble on their own.” 

Producing the full skin organ outside of a living organism would be a major leap forward for medicine.

In 2016, a team from Japan successfully created functional – and hairy – mouse skin, yet the tissue had to be transplanted onto the mouse before it fully developed.

And previous attempts to create new skin in a fully artificial environment have only been able to generate cultures of several key cell types with the hopes of combining them into a full-thickness skin in the future.

The University of Indiana’s organoid was derived from a single population of once-homogenous cells, yet represents a significant leap forward in the complexity achieved.

Jiyoon Lee, PhD, the study’s first author, highlighted the potential of his team’s technique in the statement: “My hope is that by improving skin-in-a-dish models we can greatly diminish the sacrifice of experimental animals and ultimately help patients with skin-related issues live a better life.”

One issue they may want to sort out in the near future?

“The organoids are inside-out compared to normal skin,” said Koehler.

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