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Hair Restoration Research

Study Identifies A Possible Cause of Age-Induced Hair Loss

Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis
Researchers show how the normal hair cycle (left) is disrupted by DNA damage (center),
resulting in age-induced hair follicle miniaturization (right)

We have known for decades that the incidence of male pattern baldness increases with age. New research published in the February 2016 edition of the journal Science has shed light on why this is the case. Researchers examining the role of hair follicle stem cells (HFSC) in the hair growth cycle have found that accumulated DNA damage in these cells results in the depletion of a key signaling protein and the progressive miniaturization of the hair follicle (and eventual hair loss). ((Matsumura H, Mohri Y, Binh NT, et al. Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis. Science. 2016 Feb: Vol. 351, Issue 6273, p. 613.)) The study represents a breakthrough in our understanding of the cell aging process and could open new pathways for the treatment of not only hair loss but other age-related conditions as well.

Background: The Hair Growth Cycle

At any point in time, a hair follicle exists in one of three phases:

  • Anagen Phase – this is the “growth” phase in which the hair follicle is actively producing living hair. Anagen can last from two to seven years.
  • Catagen Phase – this is a short transitional phase in which hair growth stops, the middle of the follicle constricts, and the bottom of the follicle begins to form the “club.” The follicle also separates from the bloodstream. Catagen lasts two to three weeks.
  • Telogen Phase – this is the “resting” phase in which the clubbed hair detaches from the dermal papilla and is susceptible to falling out. Telogen lasts three to four months before hair follicle stem cells initiate a new anagen (growth) phase and the cycle repeats.

Stem Cells and the Hair Cycle

Normally, hair follicle stem cells (HFSC) perpetuate the hair cycle by initiating a new anagen (growth) phase after the telogen (resting) phase. But HFSC, like all cells, age over time. Included in this aging process is damage to DNA strands inside these cells due to spontaneous errors in DNA replication or those due to exposure to sunlight and other insults. While it has been well understood that hair follicle miniaturization occurs as a person ages and that damage to genetic material contributes to the process, the exact mechanism that ties cell aging to the disruption of the normal hair cycle was unknown. The recent study examines miniaturization from cell aging and distinguishes it from miniaturization caused by the effects of DHT.

Results of the Study

The key finding in this new research is that as hair follicle stem cells (HFSC) accumulate genetic damage over time, their store of a signaling protein called COL17A1 is depleted. The depletion of this key protein forces HFSC to differentiate into a common type of skin cell called a keratinocyte. By differentiating into keratinocytes, the population of HFSC gradually shrinks, there are fewer HFSC to initiate the anagen (growth) phase, and the telogen (resting) phase is extended. With a gradually longer telogen phase and shorter anagen phase, the follicle progressively miniaturizes. Eventually, the hair-producing follicle disappears leaving a bald scalp and the keratinocytes, which no longer serve a purpose in the hair growth cycle, are ejected from the skin.1 Click here to view the graphic that illustrates this process.

The authors of the study suggest that restoring COL17A1 levels, or halting their depletion, may prevent this aging-induced hair follicle miniaturization from occurring.1

With perhaps much broader significance, the study confirms the tight linkage between the instability of genetic material in stem cells (that can be due to environmental factors) and the shrinkage and functional decline seen in many organs as they age.

Conclusion

Progressive hair loss is a pervasive problem for males as they age. However, current treatments deal, exclusively, with hormone-induced miniaturization. The discovery of the mechanism behind age-induced miniaturization may result in a new avenue for the treatment of hair loss. More research into methods of boosting levels, or preventing the depletion, of COL17A1 may yield a hair loss therapy that targets this cause of hair loss.

Further, developing a better understanding of the cell aging process may open up new avenues of research into the causes of, and potential solutions to, the age-induced decline of major organs in the body.

Read more:

Image c/o Science

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

Study Finds Low-Level Laser Therapy (LLLT) Promotes Hair Growth in Men

Evidence that low-level laser therapy (LLLT) could be used to promote hair growth, possibly by stimulating cellular function which leads to cell proliferation, a process called photobiomodulation, was first presented by Endre Mester, a Hungarian physician, in 1967. ((Mester E, Szende B, Tota JG. Effect of laser on hair growth in mice. Kiserl Orvostud 1967;19:628–631.))

Since then, many studies investigating the effects of LLLT on patients with pattern baldness (androgenic alopecia) have found a positive therapeutic effect, but most of those studies have not been properly controlled so as to rule out other, alternative, explanations for any observed hair growth.

However, a recent study ((Lanzafame R, Blanche R, Bodian A, Chiacchierini R, Fernandez-Obregon A, Kazmirek E. The growth of human scalp hair mediated by visible red light laser and LED sources in males. Lasers in Surgery and Medicine 2013; Vol. 45, Issue 8: 487-95.)) published in the journal of Lasers in Surgery and Medicine tested both the safety and effectiveness of a LLLT device in a randomized, blinded, controlled study and found that low-level laser light in the 655nm range significantly promoted hair growth in male patients with androgenic alopecia.

Specifically, 20 male subjects with pattern baldness were treated with low-level laser light for 25 minutes per day every other day for 16 weeks. After 16 weeks, a 35% increase in hair growth was observed in these subjects compared to an untreated group of males with pattern balding.

The researchers suggest that LLLT may stimulate the mitochondria in the cells of the hair follicle, leading to an increase in biological activity in those cells that promote hair growth. They also suggest that low-level light in the range used in the study might affect a hair follicle’s stem cells, which may also contribute to hair growth.

Read more about Laser Therapy for Hair Loss

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

Stem Cell Therapy Increases New Hair Growth in Males and Females with Genetic Hair Loss

According to a study ((Fukuoka H, Suga H. Hair Regeneration Treatment Using Adipose-Derived Stem Cell Conditioned Medium: Follow-up With Trichograms. EPlasty, March 26, 2015, 15:e10.)) published in ePlasty (a peer-reviewed, open access medical journal), stem cell therapy has been found to increase new hair growth in both males and females who have androgenetic alopecia (genetic hair loss).

The Study

Researchers treated a group of male and female androgenetic alopecia patients with stem cells derived from fat tissue (called adipose-derived stem cells). Additionally, to see if finasteride would confer any additional benefit along with any possible benefit of stem cell treatment, the researchers gave finasteride to half of the male patients.

After the treatment, the researchers observed a significant growth of new hair in both male and female subjects, with no significant difference between males and females. Finasteride conferred no significant additional hair growth benefit to males also receiving stem cell therapy.

The researchers concluded that injections of stem cells into the scalp of alopecia patients appears to be an effective hair loss treatment and may represent a new avenue of therapy, especially for men who do not respond well to finasteride and for women who currently have limited medical treatment options.

While there was no significant difference in hair growth between those males treated with stem cells and finasteride and those treated with stem cells alone, the researchers plan to conduct more carefully designed studies in the future to better evaluate the benefit of combining these two therapies.

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

Embryonic Stem Cell Hair Cloning May Hold The Key To Curing Baldness

New research published in the journal PLoS One found that embryonic stem cells can be used to form a type of cell that induces new hair follicle growth, and that these cells promote robust hair growth when implanted into mice.

Background

Dermal Papilla (DP) cells play a role in new hair follicle formation and in the growth of new hair. Because of this role, it was hoped that DP cells grown in the laboratory (i.e., grown in culture) could form the basis of a treatment for genetic hair loss. However, it turned out that these cultured DP cells lost their hair follicle-inducing potential too quickly to be useful in treating hair loss.

New Research

Now, however, new research has found that human embryonic stem cells (hESCs) can generate cells that are functionally equivalent to DP cells. ((Gnedeva K, Vorotelyak E, Cimadamore F, Cattarossi G, Giusto E, Terskikh V.V, Terskikh A.V. Derivation of hair-inducing cell from human pluripotent stem cells. PLoS One. 2015 Jan 21;10(1)) Like DP cells, these functionally equivalent cells can induce hair follicle formation just as readily as DP cells. But more significantly, unlike cultured DP cells, they do not lose their potential to induce hair follicle formation when grown in the laboratory. This discovery represents an important advance in developing a hair cloning technique to cure pattern baldness.

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

Hair Cloning Breakthrough with “Mass Production” of Epithelial Stem Cells

Progress towards hair cloning may have just have shifted up another gear thanks to scientists at the University of Pennsylvania and the New Jersey Institute of Technology. The breakthrough study published January 28th, 2014 is the first to show the successful transformation of adult human skin cells into quantities of epithelial stem cells necessary for hair regeneration.

The researchers, led by Dr. Xiaowei “George” Xu, started with human skin cells called dermal fibroblasts, then transformed those into a type of stem cell called induced pluripotent stem cells (iPSCs). These were then transformed into epithelial stem cells (EpSCs). This important step had never been achieved before in either humans or mice. The epithelial stem cells were combined with mouse dermal cells, that can be induced to form hair follicles, and then grafted on a mouse host. The epithelial cells and dermal cells then grew to form a functional human epidermis and follicles structurally similar to human hair follicles. The exhibits that accompany the study include photographic evidence of human hairs.

Figure 5 - Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cellsHair shafts (arrowheads) formed by induced pluripotent stem cell-derived epithelial stem cells compared to mouse hair (arrows). — Credit: Ruifeng Yang, Perelman School of Medicine, University of Pennsylvania

The main breakthrough in the study came when the research team carefully timed the addition of growth factors to the iPSCs. Previous research showed the ability for iPSCs to be transformed into a common type of cell found in the skin called keratinocytes. By timing the addition of the growth factors, they were able to turn over 25% of the iPSCs into epithelial stem cells in a little more than two weeks. This “mass production” of epithelial stem cells holds tremendous promise for the development of a hair regeneration treatment. On this development, Dr. Xu said, “This is the first time anyone has made scalable amounts of epithelial stem cells that are capable of generating the epithelial component of hair follicles.”

As noted in a University of Pennsylvania press release on the news, there are two types of stem cell that are critical in hair follicles: epithelial stem cells and dermal papillae. While this study only achieved success in the creation of epithelial stem cells, we have extensively covered Dr. Angela Christiano’s ground-breaking research into the induction of dermal papillae into hair follicles (a process she calls hair follicle neogenesis).

“When a person loses hair, they lose both types of cells. We have solved one major problem, the epithelial component of the hair follicle. We need to figure out a way to also make new dermal papillae cells, and no one has figured that part out yet,” said Dr. Xu.

Once that it is done, we must also find a way to have the epithelial and dermal components of the follicle interact before one will be able to produce cosmetically useful hair. But with each successive breakthrough, the time when a scientist can use hair cloning techniques to regenerate human hair, and the surgeon can implant them into a person’s scalp, draws ever closer.

Reference
Yang R, Zheng Y, Xu X. Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells. Nature Communications. 2014.

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

Japanese Researchers Bioengineer Hair Follicles from Stem Cells, Dermal Papillae

Japanese Researchers Bioengineer Hair Follicles from Stem Cells, Dermal PapillaeCredit: Tokyo University of Science

Japanese researchers have demonstrated that scientists can bioengineer viable, hair-producing follicles from epithelial stem cells and dermal papilla cells. Using these components, the team produced follicles that exhibit both the normal hair cycle and piloerection (the reflex contraction of a tiny muscle in the hair follicles which creates what is commonly referred to as “goose bumps”). The bioengineered follicles also developed the normal structures found within follicles and formed natural connections with skin tissues, muscle cells, and nerve cells.

The scientists used a breakthrough type of hair multiplication to achieve a functional bioengineered hair follicle. In hair multiplication, germinative cells are harvested non-surgically and then multiplied outside the body in a laboratory. These cells are then injected into the skin where they, ideally, grow into hair follicles. The Japanese research team takes this concept one step further by first combining the stem cells and dermal papillae in the laboratory to create a germ of the hair follicle. This germ is then implanted into the scalp where it grows into a viable hair follicle.

The study opens the door to treat common baldness (androgenetic alopecia) and a host of other medical conditions that can cause hair loss.

View the Hair Cloning section to read more on hair multiplication and hair cloning methods.

Reference:

Koh-ei Toyoshima, Kyosuke Asakawa, Naoko Ishibashi, Hiroshi Toki, Miho Ogawa, Tomoko Hasegawa, Tarou Irié, Tetsuhiko Tachikawa, Akio Sato, Akira Takeda, Takashi Tsuji. Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches. Nature Communications, 2012; 3: 784 DOI: 10.1038/ncomms1784

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

RepliCel Hair Cloning Research Leads To Patents, Trials In Humans

RepliCel Life Sciences; a company based in Vancouver, Canada; is investigating hair cloning techniques in order to develop a treatment for androgenetic alopecia, or common genetic hair loss.

Research conducted by the company’s scientific founders and lead scientists, Drs. Kevin McElwee and Rolf Hoffmann, has shown that a certain type of cell, called a dermal sheath cup cell, is integral in initiating the growth of mature hair follicles. ((McElwee KJ, Kissling S, Wenzel E, Huth A, Hoffmann R (2003) Cultured peribulbar dermal sheath cells can induce hair follicle development and contribute to the dermal sheath and dermal papilla. J Invest Dermatol 121: 1267–1275.)) This mechanism of follicle growth, when coupled with previous research on dermal papillae cells, is key to our understanding of hair loss and is a potential avenue for developing a treatment that could reverse hair loss.

In their 2003 study, “Cultured Peribulbar Dermal Sheath Cells Can Induce Hair Follicle Development and Contribute to the Dermal Sheath and Dermal Papilla,” the scientists found that the dermal sheath cup cells are the “reservoir” of stem cells that control both the hair growth cycle of a follicle and formation of new hair follicles.

These breakthrough findings led to RepliCel’s seeking patents for their proprietary process of isolating and preparing dermal sheath cup cells for the treatment of hair loss. Patents have been issued in Europe and Australia, and are currently pending in the US, Canada, and Japan.

In 2012, RepliCel is studying the safety and efficacy of hair regeneration from autologous dermal sheath cup cells. In the study, cells will be harvested from patients, replicated in a laboratory, and then injected into a balding area to determine if the treatment will stimulate the growth of new hair follicles in what was a bald area.

Posted by Robert M. Bernstein M.D.
Bernstein Medical In The News

Fat Cell Discovery An “Important Step” In Understanding Hair Loss

In what might be another illuminating discovery on the inner-workings of hair growth, Yale University scientists have discovered that cells from the fat layer in the skin of mice contribute to the stimulation of hair follicles.

An article by ABC News quotes the lead researcher, Valerie Horsley, saying, “The fat cells are important for hair growth. If they’re not there, the hair won’t grow. We don’t know for sure if it’s a cure for baldness, but I’m hopeful that we can get human cells to do the same as the mice cells.”

Dr. Bernstein, who was interviewed for the article, called the findings, “an interesting development in understanding why millions of people go bald.”

“It’s an important step. Mice models are not necessarily applicable to humans, but this is how we start to make discoveries,” he said.

Bernstein noted that the study’s findings don’t [directly] address genetic hair loss, in which a hormone called DHT causes hair follicles to shrink.

Dr. Horsley suggested that the next round of research should focus on finding out what cells are being effected by the fat cells, and why. She said, ”It’s very exciting because we really knew nothing about the fat in the skin. I’m hoping we can extend the research.”

Read more about research into the causes and mechanisms around hair loss in posts assigned to the tag “Stem Cells.”

Read the original article at ABCNews.com

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

Hair Loss Cure A Possible Result Of Stem Cell Communication Research

Following some new research on stem cells, and their relationship with androgenetic alopecia (genetic hair loss), an article on stem cells and the way they organize hair growth was published in the April 29th issue of the journal Science.

At issue is not the conversion of hair follicle stem cells into the progenitor cells that stimulate hair growth, as with the prior research, but the ways in which large numbers of stem cells coordinate the cycle of hair growth over thousands of hair follicles. How do all of those hair follicle stem cells know when to grow hair, and how do they know what their “neighbor” hair follicles are doing?

The researchers studied hair growth patterns in rabbits and mice and discovered that certain types of molecules, which were previously known to act as a signaling mechanism for stem cells in maintaining an individual hair follicle’s growth cycle, were also important in enabling large groups of stem cells to coordinate their activity.

The scientists found that hair stem cells coordinate their regeneration with each other with the aid of a pair of molecular activator WNT and inhibitor BMP. When WNT and BMP signals are used repetitively among a population of thousands of hair follicles across the entire skin surface, complex regenerative hair growth behavior emerges via the process of self-organization.

Perhaps more importantly, they found that the stem cell communication pathway present in rabbits and mice is far more robust than in men and women.

“When each human hair follicle wants to regenerate, it can only count on itself; it’s not getting help from other follicles,” Chuong said. “But when a rabbit hair follicle regenerates, it can count on two inputs: its own activation, and the activation signal from its neighbors. Rabbits have a very active hair growth, and that is essential for their survival in the wild.”

The article suggests that if there was a way to manage that process in humans, or “turn back on” the stem cell communication process in human hair follicles, then a treatment could be developed which would substantially increase the number of hair follicles that produce healthy hair.

Read a summary of this new research at ScienceDaily.com.

For more discussion on recent research, visit the Hair Cloning topic.

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

Progenitor Cells Could Play Key Role In Hair Loss Prevention, Cure

We recently discussed ground-breaking research that pointed to the important differences between stem cells and progenitor cells in the development of common baldness, or androgenetic alopecia (AGA).

In the March/April 2011 issue of Hair Transplant Forum International, we see a review of that research and another indication of the importance of this research in achieving the goal of being able to clone human hair.

It is now well established that, in each hair cycle, stem cells divide and generate progenitor cells, and that these progenitor cells stimulate the growth of the hair follicle. In conducting the experiment, the scientists’ original hypothesis was that the number of stem cells would be lower in scalp samples from bald areas than areas of scalp with hair. Surprisingly, they found that the stem cells were present in both samples. However, they found that the number of progenitor cells in the samples with hair was significantly higher in comparison to the bald samples. These findings suggest that it is not a reduced number of stem cells that leads to AGA, but the decreased conversion of stem cells into progenitor cells.

The research also suggests that the conversion of stem cells to progenitor cells may be the crucial mechanism that, when disrupted, leads to miniaturization of hair follicles, and common baldness. If there was a way to prevent the breakdown of stem cell conversion to progenitor cells, that could, in theory, stop the process of miniaturization and prevent androgenetic alopecia from occurring.

The study’s results and the review in the hair restoration journal indicate that, while a great deal of research must still be conducted, the scientific community is zeroing in on the cause of, and a potential cure for, genetic hair loss which has affected men and women for millennia.

For further reading on this exciting topic, here are some links:

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

Research Points to Decreased “Progenitor” Stem Cells as Cause of Male Pattern Baldness

Research published in the January 2011 issue of the Journal of Clinical Investigation (Vol. 121, issue 1) reveals another breakthrough in the medical community’s understanding of the causes of — and possible cure for — androgenetic alopecia, or common male pattern baldness. The new research shows that the presence of a certain type of cell, called progenitor cells, is significantly reduced in men with common baldness compared to men who are not bald.

An article on AOL, which calls these “faulty” stem cells the root of hair loss in men, sheds light on the findings:

Using cell samples from men having hair transplants, a team led by University of Pennsylvania dermatologist Dr. George Cotsarelis compared follicles from portions of bald scalp to follicles from scalp areas with hair.

They learned that on the same person, the bald patches had an equal number of stem cells as the patches with hair. But they did find a difference: the areas of bald scalp had a significantly lower number of a more mature type of cell, called a progenitor cell.

That finding suggests that stem cells in parts of the head without hair have malfunctioned, losing their ability to convert into progenitor cells. ((AOL, “Scientists Trace Root of Male Hair Loss to Faulty Stem Cells,” January 5th 2011))

The study showed that, contrary to conventional wisdom, it is not the total “number” of stem cells that causes hair loss. In fact, the scientists’ original hypothesis was that, “the miniaturization of the hair follicle seen in [androgenetic alopecia] may result from loss of hair follicle stem cells.” That hypothesis turned out to be inaccurate. Instead, the authors of the study indicate that the findings:

…Support the notion that a defect in conversion of hair follicle stem cells to progenitor cells plays a role in the pathogenesis of [androgenetic alopecia]. ((J Clin Invest. doi:10.1172/JCI44478.))

The study’s results suggest that further research into the mechanism for the conversion of hair follicle stem cells to progenitor cells is warranted. If scientists can devise a way to correct that mechanism, then, in theory, stem cells in men who are predisposed to have androgenetic alopecia can be converted to progenitor cells at a normal rate. That correction would, in theory, eliminate that person’s susceptibility to the hair follicle miniaturization which causes hair loss, and would effectively cure his male pattern baldness.

Progenitor Cells vs. Stem Cells

Compared to stem cells, progenitor cells are further along in the process of differentiating into their target tissue, in this case mature hair follicles. Whereas stem cells are pluripotent, meaning that they can differentiate into a number of types of cells, progenitor cells are already committed to a specific cell line. Another important difference between stem cells and progenitor cells is that stem cells can replicate indefinitely, whereas progenitor cells can only divide a limited number of times.

For further reading on this stem cells and the causes of hair loss, here are some links:

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

New Strategies for Tissue Regeneration

“She turned me into a newt! I got better…“

~ John Cleese, Monty Python and the Holy Grail

Have you ever thought that you want to be more like a newt? You might not have thought about it in those terms, but these tiny amphibians have a physical capability that human beings have dreamed about for eons: the capability of regenerating tissue. If we could tap into this capability, the possibilities for medical treatment are limitless. We could regrow an arm, a leg, a hand, repair a heart after a heart attack, or even regrow hair. Two new avenues of scientific research, discussed in an article in the New York Times, might just help us enable human beings regenerate tissue.

The Stanford Approach

For ages, it has been well known that humans do not possess the regenerative powers of lower vertebrates, such as newts and fish, but the reason has been a mystery. The researchers at Stanford University in California, working with mouse muscle cells, have begun to understand the mechanism behind the capability for certain animals to regenerate tissue.

It seems that lower vertebrates have a genetic makeup that allows their cells to multiply when tissue regeneration is needed. Since unchecked cell multiplication can also lead to tumor (cancer) formation, they also have a tumor suppressor gene known as Rb. This gene is naturally inactivated in newts and fish when they start regenerating tissue.

Mammals possess both the Rb gene and a backup, called the Arf gene, which will close down a cancer-prone cell if Rb fails to do so. […]

The Stanford team shut off both Rb and Arf with a chemical called silencing-RNA and found that the mouse muscle cells started dividing. When injected into a mouse’s leg, the cells fused into the existing muscle fibers, just as they are meant to.

It would appear then, that mammals, including humans, have regenerative capabilities normally programmed into their DNA, but over hundreds of millions of years these capabilities have been suppressed so that the more important function -– that of cancer prevention -– could operate. To clone human tissue, one would theoretically just need to deactivate the suppressor genes, but in a way that would not put the person at an increased risk of developing cancer. Of course, these genes have not yet been identified in man, nor is it known if they even exist.

The UCSF Approach

A second, but very different, approach to tissue regeneration has been taken up by Dr. Deepak Srivastava and his team at the University of California, San Francisco. Based on work by Japanese scientist Shinya Yamanaka, Dr. Srivastava successfully converted ordinary tissue cells (fibroblasts) of the mouse heart into heart muscle cells:

[Dr. Yamanaka] showed three years ago that skin cells could be converted to embryonic stem cells simply by adding four proteins known to regulate genes. Inspired by Dr. Yamanaka’s method, Dr. Srivastava and his colleagues selected 14 such proteins and eventually found that with only three of them they could convert heart fibroblast cells into heart muscle cells.

To make clinical use of the discovery, Dr. Srivastava said he would need first to duplicate the process with human cells, and then develop three drugs that could substitute for the three proteins used in the conversion process.

The drugs could then be injected into damaged areas of the heart to repair the cardiac muscle cells following a heart attack. By using heart fibroblasts to produce cardiac muscle cells, rather than using embryonic stem cells, it is possible that risk of unwanted tumor formation, often noted with stem cell therapies, can be avoided.

It is not a stretch to assume that if scientists can undo the inability of animals to grow heart muscle or limbs, we might someday be able to genetically reverse the inability of a bald person to grow hair.

View more information on hair cloning and hair cloning methods. Also view our hair cloning news and hair cloning glossary pages.

View Nicholas Wade’s NYT article, “Two New Paths to the Dream: Regeneration.” Also take a look at the diagram that accompanies the article.

Posted by Robert M. Bernstein M.D.
Hair Restoration Answers

Is Lgr5 Gene Discovery a Hair Cloning Breakthrough?

Q: I heard about the Lgr5 gene being a breakthrough in hair cloning. What’s the latest on that?

A: Many scientists feel that adult stem cells house the answer to cloning (regeneration) of hair follicles. One of the problems of hair cloning, however, is that the cells, once duplicated, “forget” that they are hair follicle cells.

It has recently been discovered that the Lgr5 gene, located in stem cells, appears to contain the “global marker” present in all adult hair follicles. If Lgr5 gene is the “calling card” of the cell, it may carry the cell lineage and shoulder the responsibility of signaling to surrounding stem cells what they are actually supposed to do as they multiply.

Recent experiments have shown that these Lgr5 cells maintain the cells ability to differentiate as hair follicles after many generations of being multiplied in the test tube and, therefore, have the potential of serving as the building blocks of entire new hair follicles. The successful exploitation of this gene would eliminate a major barrier to cloning hair.

Reference
Haegebarth A, Clevers H: Wnt signaling, lgr5, and stem cells in the intestine and skin. Am J Pathol. 2009 Mar; 174(3):715-21.

For more on how hair cloning works, visit our page on hair cloning and multiplication.

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

Hair Cloning Shows Promise in New Stem Cell Study

Alopecia areata is an auto-immune disease that causes hair loss that ranges from small circular areas on the scalp to extensive or even total baldness. When extensive, it can be a socially debilitating disease, and it can be particularly difficult when those suffering are children.

When alopecia areata is localized, i.e. there are a limited number of bald patches, the condition often responds well to cortisone injected directly direct into the scalp. When the condition is more extensive, current treatments do not have a high rate of success. A new study, using hair cloning therapy to regrow hair, shows promise for all individuals suffering from the disease.

The study — conducted by Marwa Fawzi, a dermatologist at the University of Cairo Faculty of Medicine, and reported on Bloomberg.com — used stem cells from the scalps of eight children with alopecia areata to regenerate their own hair:

The Cairo researcher took small amounts of skin from the scalps of the children, isolated the hair follicle stem cells that stimulate hair production, and grew them in the lab, increasing the number of cells. After one month, she put the cells back into the scalps of the children, with numerous injections across the bald areas of their heads. ((Kids Shunned for Hair Loss Get Help From Their Own Stem Cells by Rob Waters. Posted on Bloomberg.com, July 10, 2009))

To read more on how various cloning processes work, view the Hair Cloning Methods page.

Six months after the hair cloning treatment, an evaluation showed a 50% increase in hair in more than half of the subjects. One of them, an 8-year-old boy, grew nearly a full head of hair after being almost completely bald before treatment. The article reports that the boy is grateful that he is now able to lead a more normal life, free from social isolation over his balding scalp.

Dr. Fawzi took new skin samples and examined the hair follicles themselves and could see that the injected stem cells had migrated into the follicles. There, the stem cells stimulated the follicles to transition from a dormant phase to a hair-generating phase.

Further testing is needed and a double-blind study using a larger number of patients in planned, but the study’s success could prove to be a turning point in stem cell cloning for hair restoration. Unlike alopecia areata, where the body’s immune system attacks one’s own hair follicles, in common baldness the culprit is the hormone DHT. In spite of the differences between these two conditions, we appear to be inching closer to the use of stem cell cloning therapy in the treatment of male pattern baldness.

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

Hair Loss Gene Identified in Mice

Japanese scientists have located a gene that seems to regulate hair loss in mice. They feel that this gene may also play a role in hair loss in humans. The results of the studies were recently reported in the Proceedings of the National Academy of Sciences.

The researchers produced a strain of mice lacking in the Sox21 gene. As a result, the mice began to lose hair starting eleven days after birth. By the forth week, the mice were entirely devoid of hair. What was most interesting was that during the fourth week hair started to re-grow, but then eventually fell out starting the cycle again. These cycles were noted to repeat for as long as two years.

The scientific team is headed by Yumiko Saga of the Division of Mammalian Development at the National Institute of Genetics in Mishima, Japan. He stated that “The gene is likely involved with the differentiation of stem cells that form the outer layer of the hair shaft.”

The same Sox21 gene causing this cyclical hair loss in mice was also found in human hair shafts, so it is hypothesized that his gene might possibly be related to baldness in humans.

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

Summary: Biologists Make Skin Cells Work Like Stem Cells

Dr. Bernstein summarizes a New York Times article on stem cell research:

A major advance in regenerative medicine has recently been announced. A new technique, which can convert adult skin cells into embryonic form, has been successfully performed on interbred mice by Dr. Shinya Yamanaka of Kyoto University. The technique, if adaptable to human cells could allow new heart, liver, or kidney cells to be regenerated from simple skin cells. This tissue could potentially replace organ tissue that has been damaged due to disease. As this tissue would be formed from the patient’s own skin cells, it would not be subject to rejection by the patient’s immune system.

Prior to this discovery, the conversion of adult cells into embryonic cells was done only through nuclear transfer; the implantation of the nucleus of an adult cell into an egg. The egg then reprogrammed the adult genetic material into an embryonic form.

This new technique involves the insertion of four genes into a skin cell. These genes would then complete the reprogramming of the nucleus of the skin cell into embryonic form, just as the egg had in nuclear transfer.

If adaptable to human cells, this could provide a simple, inexpensive and politically uncontroversial technique for regenerating stem cells. It should eliminate the ethical debates regarding stem cell research.

But this discovery does not mean that cloning will be available anytime soon. There are many obstacles which must be overcome prior to its implementation. The most immediate problem is discovering if this technique, which has been performed only in mice, can be used successfully with human cells. Another problem is that the mice that were used in the experiment were interbred, something obviously not acceptable for humans. In addition, the cells must be infected with a gene-carrying virus, a process that may not be safe for humans. Finally, two of the four genes which are needed to begin this regenerative process are carcinogenic (potentially cancer forming). In fact, 20% of Dr. Yamanaka’s mice died of cancer.

Although scientists cannot begin to predict when these considerable problems might be overcome, they are still confident in this advancing breakthrough and that these obstacles will someday be overcome.

Reference: Biologists Make Skin Cells Work Like Stem Cells by Nicholas Wade, NYT, June 7, 2007

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

Skin Cells Substitute for Embryonic Stem Cells in Cloning Research

The advantage of using embryonic stem cells in cloning research, organ transplantation, and in finding cures for disease, is that these cells are basically “unprogrammed.” This means that the stem cell has not yet determined what it will grow to become so, in theory at least, scientists can manipulate them into becoming anything that they are programmed to be.

Two teams of scientists working independently (Kazutoshi Takahashi and Shinya Yamanaka at Kyoto University, Japan and James Thompson’s team at the University of Wisconsin) announced that they had successfully replicated the biological abilities of the embryonic stem cell using only skin cells. Called “induced pluripotent stem cells” these former skin cells were programmed to become other types of cells, acting in the same way as the embryonic stem cells.

This transformation was accomplished by introducing four basic genes into skin cells, via a viral carrier. These genes cause the adult skin cells to revert and become the equivalent of embryonic stem cells. The breakthrough is in the ability to “unprogram” skin cells so that they revert to cells that have the same response and abilities as embryonic stem cells.

The debate regarding embryonic stem cells has been focused on the harvesting of the cells. A fertilized embryonic egg is allowed to mature until it formed blastocysts. These blastocysts contain the newly formed stem cells. When these stem cells are removed, the embryo is destroyed. If skin cells can be successfully converted to stem cells, this could negate the ethical questions of the use of embryonic stem cells and produce a large amount of readily available stem cells for research.

Caution must be taken with this new technology. For example, one of the genes used to unprogram the skin cells is carcinogenic (cancer-causing).

Research must also be done to verify that these reprogrammed cells don’t have subtle differences between themselves and true embryonic stem cells.

Although the ability to “unprogram” skin cells to form pluripotent stem cells is a significant breakthrough, it is important to stress that this is still a research tool and it will take quite some time before it is known if these cells can truly substitute for stem cells in the treatment of disease.

References:

Kazutoshi T, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S: Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors: Cell (2007), 131, 1-12.

Kolata G, Scientists Bypass Need for Embryo to Get Stem Cells, New York Times, 2007; A-21:23.

Posted by Robert M. Bernstein M.D.
Hair Restoration Research

Summary: Hair Follicle Regeneration in Adult Mouse Skin After Wounding

Dr. Bernstein summarizes an article on stem cells that was published in the journal Nature:

This study demonstrates that after wounding the skin of an adult mouse, an embryonic-like change in the epidermal cells outside of the hair follicle stem cells can be induced to form new hair follicle stem cells. In other words, these cells originate from epidermal skin cells in the wound, but then are able take on the characteristics of hair follicle stem cells and actually produce hair. These regenerated hair follicles establish a stem cell population that can produce a hair shaft and continue through all stages of the follicular cycle. The research suggests that these regenerated hair follicles grow new hair through the introduction of Wnt proteins.

The technology, developed at the University of Pennsylvania School of Medicine, has been licensed by Follica Inc. a privately held medical device company.

Reference: “Hair Follicle Regeneration in Adult Mouse Skin After Wounding,” Ito, M., et al. Nature 447, 316-320, May 17, 2007

Posted by Robert M. Bernstein M.D.
Hair Restoration Answers

How Are Hair Cloning, Hair Multiplication, and Follicular Neogeneis Different?

Q: What is the difference between hair cloning, hair multiplication, and follicular neogeneis? I have read about these terms on the internet and am completely confused.

A: Cloning generally refers to the multiplication of fetal stem cells or embryonic tissues. “Hair cloning”, as the term is generally used, involves the multiplication of adult tissue cells that are used to induce the formation of new hair, so the term is not exactly accurate.

“Hair multiplication” refers to the multiplication of adult hair structures. This model is not actively being pursued since the hair follicle is too complex to be simply cultured in a tube. Instead individual cells called fibroblasts are removed from the scalp multiplied in tissue culture and then these are injected back into the scalp in the hope that they will induce intact follicles to form.

“Follicular neogeneis” is probably the best of these terms, as it describes the formation of new follicles derived from inducer cells that are cultured and then injected into the scalp. It is the preferred term of Ken Washenik at Aderans. Interctyex uses the term “follicular cell regeneration” for its technology.

Posted by Robert M. Bernstein M.D.
Hair Restoration Answers

What is Difference in Hair Cloning Techniques Studied by Aderans and Intercytex?

Q: I know that both Aderans and Intercytex are doing research with cloning hair. Is there any difference in their approaches?

A: Aderans is using the “two-cell” approach. They feel that the best way to produce viable hair follicles is to use a combination of inducer cells and responder cells. Each would be multiplied separately and then injected together into the skin. The inducer cells are follicular fibroblasts and lie at the base of the hair follicle. The responder cells are keratinocytes. They feel that the combination of cells will have the best chance of producing clinically useful hair.

Intercytex prefers a one-cell approach. Their researchers feel that when the cultured inducer fibroblasts are injected into the skin there will be enough existing cells in the skin to produce a cosmetically viable hair. In their experimentation, Intercytex uses a new animal model, termed the “flap graft” model, that involves the implantation of cultured dermal papilla cells with keratinocytes placed under a flap on the back of hairless mice. Later the flap is exteriorized (turned over), allowing the hair to grow normally. Exactly how this will be applied to clinical use in humans is not clear.

A completely different view is held Dr. Ralf Paus at the University of Luebeck in Germany. He feels that there are already enough stem cells in the bald scalp and that the key to hair re-growth is to target key elements in the hair cycle. He feels that topically applied inhibitors of catagen (the resting phase of the hair cycle), exogen (the formation of an empty hair follicle), or inhibitors of the terminal-to-vellus transformation (the process of a hair shrinking in size under the influence of DHT and referred to as miniaturization) will the most effective way to go.

Finasteride and dutasteride are drugs that work in this way, but are clearly not very effective in stimulating new growth. He also feels that an anagen inducer, along the lines of a minoxidil-type medication has a better chance of success then the stem cell targeting strategies described above. In these cases one would, in a sense, rejuvenate dormant hair follicles rather than induce new ones to grow.

Read about Hair Cloning Methods

Posted by Robert M. Bernstein M.D.



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