Hair Loss and Baldness: The Secrets Hidden in Hair Follicle Stem Cells

When hair loss and baldness meet stem cell technology, perhaps medical problems become miracles.

Familiar with the working law of hair

Hair follicles are the factories that produce hair. As soon as the dermal papilla cells at the root of the hair give instructions, the hair mother cells begin to divide repeatedly, accumulate keratin, and then keratinize and accumulate hair. Each hair will not grow endlessly, but has a growth cycle.

The growth cycle of normal hair includes three stages: anagen phase, degenerative phase (Catagen phase) and resting phase (Telogen phase).

normal hair growth cycle

The anagen phase lasts 2-6 years and is a critical stage for hair growth. At this time, hair mother cells are in a state of highly active division, but they are particularly sensitive. Endocrine disorders, high hormone secretion, stress, medication, burns, trauma, disease and malnutrition can all stop normal hair growth.

During the catagen phase, less than 1% of hair follicle stem cells stop working (growth), which generally lasts for about 1-2 weeks. During this period, cell division slows down, hair roots shrink, and hair gradually moves away from the hair roots to the upper layer of the scalp.

In the telogen phase, about 10% of the stem cells rested (rested). The time is about 5-6 weeks, during which the hair will fall off automatically.

After sufficient rest, the stem cells return to the progenitor phase and begin a new cycle.

A healthy adult has a total of about 100,000 hairs, most of which are in the anagen phase. Under normal circumstances, it is normal for a healthy adult to lose 50-100 hairs naturally every day on average.

Familiarize yourself with the typical types of hair loss

To know it, but also to know why. Broadly speaking, the typical human hair loss has the following types, please see the four brothers of the hair loss family:

1. The boss yells: androgenetic alopecia (Mediterranean alopecia)

Male baldness, also known as Seborrheic alopecia, is generally an ancestral Mediterranean hairstyle. As the name suggests, it is also the most common hair loss in men. This is mainly because the testosterone in the androgen is upgraded to dihydrotestosterone, which gives the hair follicles an order: get off work!

As a result, the hair follicles began to shrink, from 3-4 healthy hairs in a hair follicle, to 1-2 hairs, or even fluff. Females may also be "bald" due to male hormones, but the transitional thinning occurs from the center of the top of the head to the sides, the hair follicles of the scalp shrink, and the overall hair volume decreases. The oral medications finasteride and dutasteride lower DHT levels and reduce hair loss.

2. The second child is called: Alopecia areata (ghost shaved head)

The appearance of alopecia areata is always sudden and irregular, commonly known as "ghost shaving". This is mainly related to genetics, autoimmunity, endocrine disorders, it feels like the stem cells in that area are suddenly fired!

However, in many cases, if you adjust your work and rest, adjust your immunity and endocrine, you will recover slowly (it will take about 6 months).

3. The third child is called: telogen effluvium

Due to various stimulating factors, the number of hair follicles in the telogen phase increases, leading to an increase in the amount of hair loss in the later period, which is telogen effluvium. For example, postpartum hair loss is a very typical situation, because the estrogen is too high during pregnancy, the growth period of hair follicles is prolonged, and the time to enter the resting period is delayed. After giving birth, the secretion of estrogen is normal, but the hair follicle stem cells are exhausted, and then they take a collective rest for a period of time.

Therefore, postpartum hair loss is also a common phenomenon, and most of them will recover slowly with their physical conditions. After enough rest, you should go to work.

4. The fourth child is called: hair loss during growth period

There are unpredictable things in the sky, and people have misfortunes and blessings. Hair follicles are attacked by antineoplastic drugs or toxic substances, which can cause rapid hair loss.

Such as chemotherapy. Suddenly, the hair follicle stem cells completely stopped working, which caused a large amount of hair loss. Basically, this situation is saying goodbye to the full head of hair.

What exactly are hair follicle stem cells?

The so-called hair follicle stem cells (HFSC) are the primitive cells in the hair follicle, which are a kind of adult stem cells. Both human hair and body hair grow from hair follicles. However, the hair follicle stem cells responsible for hair growth are usually in a dormant state, but will be activated and divided rapidly in a new round of hair growth cycle. When adjacent parts are damaged, hair follicle stem cells can migrate out of the protuberance where they were originally located and participate in the repair of the damaged part.

Hair Follicle Stem Cells

The hair follicle is the basic unit of the hair, and the hair is formed by the growth and differentiation of the cells in the hair follicle. A group of hair follicle stem cells live in each hair follicle, supplying new cells to the growing hair follicle. Hair follicle stem cells can also differentiate into sebaceous glands, which produce the oil the skin needs.

Hair follicle stem cells colonize the hair follicle bulge and have the characteristics of stem cells, including multilineage differentiation potential, potential high proliferation ability and the ability to maintain cell quiescence. There is a stem cell pool in the bulge area of ​​the hair follicle, which is the stem cell pool of keratinocytes, melanocytes and mesenchymal dermal cells. Therefore, hair follicle stem cells play an important role in each proliferation cycle of the hair follicle.

Hair follicle stem cells are easier to obtain than stem cells from other organs. Hair follicle stem cells are likely to be contained in the hair we pluck out. If you master the technology of in vitro culture of hair follicle stem cells, you can carry out a large number of cultures.

How to Isolate and Characterize Hair Follicle Stem Cells

Preparation of Hair Follicle Stem Cells by Enzyme Digestion

After talking about the basic knowledge of hair follicles and hair follicle stem cells, I will talk about how to obtain these possible hair follicle stem cells.

1. Starting from the method of isolation and preparation of hair follicle stem cells

General traditional ideas: enzymatic digestion full culture method and tissue patch method. But this method is to obtain mixed cells, and a family can have everything, as long as it can grow. What we want are relatively pure hair follicle stem cells. Therefore, according to the different adhesion ability and speed, the researchers invented the differential speed adhesion method to further purify the cells. Later, using the specific markers of hair follicle stem cells, researchers invented the immunomagnetic bead method and flow sorting method. The key to this method is to find specific markers. You are all about me.

As a result, the general separation and preparation method of hair follicle stem cells was released, as shown in the figure below.

Summary of Hair Follicle Stem Cell Preparation Methods

2. Identification and sorting markers of hair follicle stem cells

After the cells are prepared, how do you know if they are the hair follicle stem cells you want? Identification required! Like other stem cells, there are two types of markers for hair follicle stem cells. Markers located in the cytoplasm and nucleus are mainly used for cell identification; markers located on the surface of the cell membrane are mainly used for identification and sorting of stem cells.

According to hair follicle stem cell markers, many scholars have obtained hair follicle stem cells of a certain purity by methods such as flow cytometry and immunomagnetic beads, and successfully cultured them in vitro.

Application ideas of hair follicle stem cells

Hair is differentiated from hair follicle stem cells in the bulge area of ​​the hair follicle. During this differentiation process, hair follicle stem cells are naturally regulated by some signals in the surrounding environment, which in turn affects hair development or regeneration. Therefore, if you want to improve hair loss and hair growth, hair follicle stem cells are the key.

Xiaoxian believes that if hair follicle stem cell technology is to be used as the core to improve hair loss, from a technical perspective, there are the following possible product/technique/project ideas:

Clinical research idea one:

Hair follicle stem cell transplantation. Collect a small piece of skin (such as the back of the head) from the thick hair, separate and prepare hair follicle stem cells, and then inoculate the hair follicle stem cells to the hair loss site through local transplantation (transplantation methods include small chamber method, cell mixed injection method, etc.), to promote the regeneration of damaged hair follicles Repairs and reduces hair loss.

Clinical research idea two:

Hair follicle stem cell exosome injection. Exosomes are isolated from the culture supernatant of hair follicle stem cells and used for injection/microneedling to the hair loss site to improve hair loss and promote new hair growth.

It has been reported that the secreted protein of mesenchymal stem cells can promote skin regeneration and hair regeneration, and the conditioned medium (CM) of MSCs from various sources (umbilical cord, bone marrow, fat, etc.) is rich in various cell growth factors and exosomes, have the effect of promoting hair growth, and can promote the proliferation of dermal papilla cells (DPC) and human epithelial keratinocytes (HEK) present in hair follicles.

Exosomes isolated from the conditioned medium of hair follicle stem cells may be more effective.

Clinical research idea three:

Follicular unit transplantation. Combined with tissue engineering, hair follicle stem cells and hair papilla cells ( DPC ) are inoculated into the acellular matrix to form a "regenerated hair follicle primordium", and a double-layer tissue engineered skin is constructed, which is transplanted into the hair loss scalp to promote the formation of mature hair follicles.

This idea has also been tried before. Takashi Tsuji's team from the Institute of Physical and Chemical Engineering in Japan isolated the "epithelial stem cells (hair follicle stem cells)" and "mesenchymal stem cells (hair papilla cells)" in mouse hair follicles and cultured them in vitro into "regenerated hair follicle primordia". The cultured primordium tissue was transplanted to the back of nude mice, and hair grew successfully. This astonishing achievement was published in "Scientific Reports" in 2012. The most amazing thing is that these hairs are not transplanted, they are created through hair follicle stem cell technology.

About Shiseido's "hair follicle stem cell" technology

When it comes to hair follicle stem cell technology in Japan, we have to talk about Shiseido. Usually, everyone calls Shiseido's technology hair follicle stem cell technology, which is wrong. In fact, it is not a real stem cell technology, and it is not independently developed by Japan. The technology is from the Canadian company Replicel. The official website calls it DSC Cell Therapy (DSC cell therapy) or RCH-01 technology. RCH-01 is an autologous cell therapy for male pattern baldness using dermal sheath goblet cells (DSC) isolated from hair follicles. Dermal sheath goblet cells were isolated from the patient's posterior occiput, expanded in vitro, and reinjected into the patient's alopecia area. It has a certain effect on mild hair loss. Yes, if the hair follicle is not closed, it will have no effect if the hair follicle has been closed.

Challenges and Prospects of Hair Follicle Stem Cell Technology

If a culture system that truly simulates the growth environment of hair follicles in vivo can be established in vitro, and the biological characteristics of dermal papilla cells and hair follicle stem cells can be maintained, then the reconstruction of mature hair follicles in vitro and the resulting hair and sebaceous glands are very promising.

No matter which method is used, it is a technology that entrusts countless people to dream of hair regeneration, and hopes to enter clinical practice one day earlier. The future is bright and tortuous , and everything is waiting for technological development .

Baldness - the secret hidden in the cells

Scientists discover the originator of "baldness" and "white hair"!

In the past few days, scientists have not only identified the cells directly related to the generation of gray hair, but also revealed the specific molecular mechanism that causes hair graying in these cells.

During the course of their research, the scientists at UT Southwestern Medical Center had to work with the vesicle substrate in cells. Although this is the darkest and unknown place in the cell, the normal functions of stem cells, progenitor cells and melanocytes all rely on this seemingly useless cellular structure to do their most important things, such as Melanin that makes your hair shiny and shiny.

Interestingly, this project to help people dye hair and prevent hair loss actually originated from a cancer research project. Scientists were studying a condition called neurofibromatosis type 1, a rare genetic disorder that causes tumors to grow on nerve tissue.

"While this project started out to understand how certain types of tumors develop," the authors said, "we ended up figuring out questions like why hair turns gray.

"Based on these studies, we hope that in the future we will be able to develop a specific drug, or safely deliver the necessary gene to the hair follicle to restore the hair's luster."

The article corresponding to this study was published in the latest online Genes & Development magazine, entitled "Identification of Hair Shaft Progenitors That Create a Niche for Hair Pigmentation."

"We found that hair follicle stem progenitor cells at the base of the follicle are distinct from follicular epithelial cells and that these cells express a transcription factor called KROX20," the authors write. Experiments show that downregulation of this transcription factor leads to hair loss growth arrest, KROX20-expressing cells are really indispensable for your black hair."

The researchers found that during the specialization of skin cells into hair roots, the KROX20 protein will show more interconnections with nerve cells, and these hair progenitor cells will further produce another extremely important substance in the process of specialization—— - Stem cell factor (SCF).

" SCF expression is critical for the maintenance of hair progenitor cells, melanocyte differentiation, and hair pigmentation, " the researchers added .

When the scientists deleted the SCF gene in hair progenitor cells in a mouse model, the experimental mice experienced short-term graying of their hair. When the apoptosis of KROX20-expressing cells is exhausted, the mouse's hair will also fall out, and no new hair will grow.

If there is a connection between KROX20 protein and SCF-expressing cells, they must also interact with melanin-producing cells to jointly promote hair growth and blackening.

"Our findings reveal intrinsic factors that regulate hair growth and pigmentation, the progenitor cells of the hair matrix that actually determine whether you have hair on your head or not," the article's authors added.

Now, researchers at UT Southwestern Medical Center will try to figure out whether genes encoding KROX20 and SCF in cells stop working properly as mammals age, leading to the gray hair and hair loss found in older adults, as well as males. Hereditary baldness.