transplants Archives - Sanford Burnham Prebys
Institute News

SBP’s Alexey Terskikh advances hair growth research

AuthorMonica May
Date

August 16, 2018

Three years ago, Alexey Terskikh, PhD, associate professor in Sanford Burnham Prebys Medical Discovery Institute’s (SBP’s) Development, Aging and Regeneration Program, published a groundbreaking study showing that stem cells could be used to grow hair.

This discovery could help more than 80 million men, women and children in the United States experiencing hair loss. Across cultures, personal identity is connected with hair. As a result, hair loss often affects emotional well-being and self-esteem. There is clear interest in the technology: Our 2015 story on this finding remains our blog’s most-read article. 

Since then, Terskikh and his team have been working hard to advance this technology. We caught up with Terskikh to learn about his progress—and how far away the research remains from human studies. 

Alexey Terskikh
     Alexey Terskikh, PhD

Could you fill us in on your work since 2015?

For the past three years, my team and I have been working to overcome several obstacles to the technology’s real-world use. We’ve made progress on multiple fronts, summarized below:

Generating unlimited cells 
Instead of embryonic stem cells, which are difficult to obtain, our method now uses induced pluripotent stem cells (iPSC), which are derived from a simple blood draw or skin sample. iPSCs allow us to create an unlimited supply of cells to grow hair. Not having enough hair is one reason current transplants don’t work, so this is a critical advance.

Creating a natural look
Hair actually grows in a specific direction, so it’s important to control the orientation of hair growth to achieve a natural look. Your hair stylist is familiar with this!

We’ve found a solution—3D biodegradable scaffolds—and partnered with leading scientists in the field to advance our project. The scaffold allows us to control the number of cells transplanted, their direction and where they are placed.

Helping the transplant “take”
The scaffold has a second job of helping seed hair follicles. Skin is a good barrier—that’s its job—so we needed something to help the transplant “take.” The scaffold provides the “soil” from which the hair can grow. 

Hair-generating cells in mouse skin
Hair-inducing human cells (red)
generated from iPSC present within hair
follicles grown in mouse skin. 

I understand you have formed a company based on this research. Can you tell us more? 

Yes, we have formed a company this year and assembled a great team with the expertise needed to move the technology forward. These experts include hair transplantation specialists, experienced entrepreneurs and experts in manufacturing cells at large scale (not a trivial endeavor). 

While hair loss affects people’s self-esteem and self-image, it isn’t life threatening, so it’s not a top priority for many funding agencies. Forming a company gives us a vehicle for raising capital to advance this technology.

Do you know how the stem cell–generated hair will look? Can you control hair color? 
We hope that stem cell–generated hair will look exactly as the original hairs that have been lost. Of course, it will take some time to grow a “perfect” hair, but we believe this should be possible in the long run.

Has anything surprised you during this process? 
I expected to hear from young and older men, but I was surprised by the number of women who reached out to express interest in our research. I received about an equal number of emails from women. Pregnancy, menopause and ovarian conditions may all cause hair loss for women. 

Most heartbreaking were emails from parents of children with alopecia, a condition where a child cannot grow hair. As you can imagine, hair loss at such a young age can affect relationship formation and self-image. All these emails continue to motivate me to keep advancing this research as quickly as possible.

What work needs to be done before you can test this on humans? How far away are we from this product being used on humans?

The good news is that we’ve resolved the biological mystery of hair growth using stem cells. Now, it is mostly an engineering exercise: how to get robust and properly oriented hair growth. 

Before we can discuss human studies with the U.S. Food and Drug Administration (FDA), we need to complete safety and tumorigenicity tests in mice. We are performing these tests very soon. 

Provided we have the proper funding, we expect it will take two years before we can start discussions with the FDA.

Assuming all goes as planned and the FDA approves a first-in-human study, will everyone be eligible for the trial? 

At that point we will work very closely with clinical experts in the field to determine which individuals are most likely to benefit from this research and should be involved in the trial. 

How did you first get started on this research? 

That’s actually a funny story. My father—who is a scientist—wanted to stay more in touch, so we decided to do a joint project. I was researching stem cells, and he was researching skin follicles, so we ended up here! If you look at the paper, you’ll see two authors who have the same last name—him and me. 

Interested in keeping up with SBP’s latest discoveries, upcoming events and more? Subscribe to our monthly newsletter, Discoveries.

Institute News

Rebooting the immune system after a bone marrow transplant

AuthorJessica Moore
Date

August 30, 2016

After a bone marrow transplant, it can take months for the number of T cells to reach healthy levels. Because T cells are crucial for launching an effective immune response, this leaves patients—usually cancer survivors whose immune systems were knocked out by chemotherapy—vulnerable to infections for longer. However, new research, to which Carl Ware, PhD, professor and director of the Infectious and Inflammatory Disease Center, contributed, identifies a novel target for immunotherapeutics to shorten this recovery time.

“This study shows that the lymphotoxin β receptor controls the entry of T cell progenitors into the thymus, the organ where T cells mature,” said Ware. “Future compounds that activate this receptor may help transplants give rise to functional T cells faster.”

Within the overall immune response against invading bacteria, viruses, and other pathogens, T cells are the field officers and special forces. Helper T cells send chemical signals to get other parts of the immune system involved, and cytotoxic T cells recognize and kill infected cells directly. They’re ‘trained’ to distinguish threats from the cells of the body in the thymus, where T cell progenitors that react to normal, uninfected cells are eliminated.

Publishing in the Journal of Immunology, the team, led by William Jenkinson, PhD, and Graham Anderson, PhD, of the University of Birmingham, looked at the importance of various receptors in letting T cell progenitors into the thymus, and found that only the lymphotoxin β receptor was required.

Significantly, the researchers also showed that stimulating the lymphotoxin β receptor boosted the number of transplant-derived T cells.

“Post-transplantation, T cell progenitors can struggle to enter the thymus, as if the doorway to the thymus is closed,” said Anderson. “Our work points to a way to ‘prop open’ the door and allow these cells to enter and mature.”

Ware and his lab have made many contributions to understanding how the lymphotoxin β receptor, as well as other related receptors, affect immunity and inflammation.

“The lymphotoxin β receptor is important not only in the thymus, but also at sites of inflammation and infection,” Ware added. “Further investigation of the effects of activating it throughout the body will determine whether this treatment approach is feasible, or perhaps should be targeted to the thymus.”

The paper is available online here.

Institute News

Scientists find optimal method for generating regulatory T cells to treat autoimmune disease

Authorjmoore
Date

March 11, 2016

While we normally think of T cells as recognizing invaders, their roles are more complex. For example, some T cells, called regulatory T cells (Tregs) suppress conventional T cells’ immune responses. Because conventional T cells can escape normal controls and drive autoimmune diseases such as rheumatoid arthritis and type 1 diabetes, as well as rejection of transplants, Tregs are increasingly viewed as a way to rein in autoimmune diseases. Continue reading “Scientists find optimal method for generating regulatory T cells to treat autoimmune disease”

Institute News

Using stem cells to grow new hair

Authorsgammon
Date

January 27, 2015

In a new study, Sanford-Burnham researchers have used human pluripotent stem cells to generate new hair. The study represents the first step toward the development of a cell-based treatment for people with hair loss. In the United States alone, more than 40 million men and 21 million women are affected by hair loss. The research was published online in PLOS ONE.

“We have developed a method using human pluripotent stem cells to create new cells capable of initiating human hair growth. The method is a marked improvement over current methods that rely on transplanting existing hair follicles from one part of the head to another,” said Alexey Terskikh, PhD, associate professor in the Development, Aging, and Regeneration Program. “Our stem cell method provides an unlimited source of cells from the patient for transplantation and isn’t limited by the availability of existing hair follicles.”

The research team developed a protocol that coaxed human pluripotent stem cells to become dermal papilla cells. They are a unique population of cells that regulate hair-follicle formation and growth cycle. Human dermal papilla cells on their own are not suitable for hair transplants because they cannot be obtained in necessary amounts and rapidly lose their ability to induce hair-follicle formation in culture.

“In adults, dermal papilla cells cannot be readily amplified outside of the body and they quickly lose their hair-inducing properties,” said Terskikh. “We developed a protocol to drive human pluripotent stem cells to differentiate into dermal papilla cells and confirmed their ability to induce hair growth when transplanted into mice.”

“Our next step is to transplant human dermal papilla cells derived from human pluripotent stem cells back into human subjects,” said Terskikh. “We are currently seeking partnerships to implement this final step.”

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