Researchers grow hairy skin from human stem cells

 Dr. Jiyoon Lee (left) and Dr. Karl Koehler (right), Indiana University School of Medicine

For years the idea of being able to regrow hair has been the domain of cheesy, middle-of-the-night TV infomercials. Now two researchers may have found a way to actually make it happen, and their work could have implications far more important than helping bald men.

Building on years of research, Dr. Jiyoon Lee and Dr. Karl Koehler from the Indiana University School of Medicine were able to use human stem cells to grow hair on skin. The complex skin model was developed by using pluripotent stem cells, a kind of stem cell that can become virtually any kind of cell in the body.

To do this, Dr. Lee, Dr. Koehler, and a team of researchers incubated the human stem cells for 150 days. During this time, the cells formed a ball shaped cluster of cells called a skin organoid. The interior of the organoid is similar to the top layer of skin, known as the epidermis, and the outside is similar to the bottom layer, known as the dermis.

In a press release, Dr. Koehler describes the skin organoid and the process in more detail.

“We’ve developed a new cooking recipe for generating human skin that produces hair follicles after about 70 days in culture. When the hair follicles grow, the roots extend outward radially. It’s a bizarre-looking structure, appearing almost like a deep-sea creature with tentacles coming out from it.”

After the skin organoid was formed, the researchers tested if it could be integrated onto the skin of nude mice by performing skin grafts. The results were remarkable as more than half of the organoids that the scientists engrafted on the mice grew human hair follicles. The skin organoid developed is similar to fetal facial skin and hair.

This skin organoid model has great potential in terms of helping with drug or gene therapies for skin disorders or recreating the earliest stages of skin cancer formation.

In the same press release, Dr. Lee discusses the potential their findings have for reconstructive purposes.

“This could be a huge innovation, providing a potentially unlimited source of soft tissue and hair follicles for reconstructive surgeries.”

The full results of this study were published in Nature.

Targeting hair follicle stem cells could be the key to fighting hair loss

Chia Pets make growing hair look easy. You might not be familiar with these chia plant terracotta figurines if you were born after the 80s, but I remember watching commercials growing up and desperately wanting a “Chia Pet, the pottery that grows!”

My parents eventually caved and got me a Chia teddy bear, and I was immediately impressed by how easy it was for my bear to grow “hair”. All I needed to do was to sprinkle water over the chia seeds and spread them over my chia pet, and in three weeks, voila, I had a bear that had sprouted a lush, thick coat of chia leaves.

These days, you can order Chia celebrities and even Chia politicians. If only treating hair loss in humans was as easy as growing sprouts on the top of Chia Mr. T’s head…

Activating Hair Follicle Stem Cells, the secret to hair growth?

That day might come sooner than we think thanks to a CIRM-funded study by UCLA scientists.

Published today in Nature Cell Biology, the UCLA team reported a new way to boost hair growth that could eventually translate into new treatments for hair loss. The study was spearheaded by senior authors Heather Christofk and William Lowry, both professors at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Christofk and Lowry were interested in understanding the biology of hair follicle stem cells (HFSCs) and how their metabolism (the set of chemical changes required for a cell to sustain itself) plays a role in hair growth. HFSCs are adult stem cells that live in the hair follicles of our skin. They are typically inactive but can quickly “wake up” and actively divide when a new hair growth cycle is initiated. When HFSCs fail to activate, hair loss occurs.

A closer look at HFSCs in mice revealed that these stem cells are dependent on the products of the glycolytic pathway, a metabolic pathway that converts the nutrient glucose into a metabolite called pyruvate, to stimulate their activation. The HFSCs have a choice, they can either give the pyruvate to their mitochondria to produce more energy, or they can break down the pyruvate into another metabolite called lactate.

The scientists found that if they tipped the balance towards producing more lactate, the HFSCs activated and induced hair growth. On the other hand, if they blocked lactate production, HFSCs couldn’t activate and new hair growth was blocked.

In a UCLA news release, Lowry explained the novel findings of their study,

“Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells. Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.”

New drugs for hair loss?

In the second half of the study, the UCLA team went on the hunt for drugs that promote lactate production in HFSCs in hopes of finding new treatment strategies to battle hair loss. They found two drugs that boosted lactate production when applied to the skin of mice. One was called RCGD423, which activates the JAK-Stat signaling pathway and stimulates lactate production. The other drug, UK5099, blocks the entry of pyruvate into the mitochondria, thereby forcing HFSCs to turn pyruvate into lactate resulting in hair growth. The use of both drugs for boosting hair growth are covered by provisional patent applications filed by the UCLA Technology Development Group.

Untreated mouse skin showing no hair growth (left) compared to mouse skin treated with the drug UK5099 (right) showing hair growth. Credit: UCLA Broad Stem Cell Center/Nature Cell Biology

Aimee Flores, the first author of the study, concluded by explaining why using drugs to target the HFSC metabolism is a promising approach for treating hair loss.

“Through this study, we gained a lot of interesting insight into new ways to activate stem cells. The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss. I think we’ve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; I’m looking forward to the potential application of these new findings for hair loss and beyond.”

If these hair growth drugs pan out, scientists might give Chia Pets a run for their money.

Pleasant surprise reveals molecular insights about graying and balding hair

A lesson that every lab researcher learns early in their career is that experiments often don’t give you the results you expect. But that’s not always a bad thing. Sometimes surprising results can lead to new insights or can even steer your research in completely new, exciting directions.

That’s what happened to scientists at the University of Texas Southwestern Medical Center. What started out as a project to better understand a genetic disorder – called neurofibromatosis – that causes benign tumor growth on nerve cells, turned into new discoveries about the cellular basis for graying and balding hair – at least in mice.

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Starting at 30 days after birth (P30, upper right picture), mouse lacking the SCF gene (top mouse in each picture) gradually loses hair pigment while hair color of control mouse remains unchanged. Photo: Fig 1A, Genes Dev. 2017 May 2.

The team was studying neurofibromatosis in mouse cells that produce Krox20, a protein which plays a role in the development of nerve cells. Krox20, in turn, stimulates the production of another protein called Stem Cell Factor (SCF). With some genetic engineering tricks, a mouse strain lacking SCF specifically in these Krox20-producing cells was bred to uncover SCF’s impact on neurofibromatosis.

HairAnatomy

Hair production and pigmentation occurs in hair follicle. Image: Shutterstock

But the researchers couldn’t help noticing something else: as reported in Genes and Development, just a month after birth, all 20 mice had graying fur and by nine months, their fur was completely white. Another set of mice was bred to lack Krox20-producing cells. The resulting animals completely lacked hair. Further experiments determined that the Krox20-producing cells in the hair follicle were stem cell-like progenitor cells that give rise to the cells responsible for hair production and pigmentation.

Piecing the data together, the researchers created a visual model of the hair follicle in which the progenitor cells maintain a steady supply of hair-producing cells with Krox20 playing a critical role. And the SCF produced by those cells allows the uptake of hair pigment called melanin, from nearby melanocyte cells also found in the hair follicle.

This model suggests that as we age, something causes a reduction in SCF in the hair follicle which leads to graying hair. The model also suggests that thinning hair, which is quite common in both men and women, is triggered by a reduction in the number of progenitor cells in the follicle.

Given that the treatment of hair loss and graying are multi-billion dollar industries, it’s no surprise that this story got a lot of attention in the press. Based on the titles of some of those news articles, you’d think new, game-changing hair products are just around the corner. In reality, this research is at a very early stage and will require many years of follow up experiments to figure out if and how commercialization of the technology is possible.

Still, as lead scientist Dr. Lu Le explains in a press release, the team has a vision for what their ultimate goal might look like:

“With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems.”