Summary: Can hair follicles really regenerate? What is the principle that allows hair follicles to regenerate? The Yale team discovered a new molecular signal that induces hair follicle formation. In the near future, hair follicle regeneration may be really feasible.
Hair loss is already a worldwide problem, with more than 250 million people suffering from hair loss on the mainland alone. According to the "2020 National Health Insight Report", hair loss problems ranked in the top 10 list of national health. In general, it is normal to lose 50-100 hairs per day, but if it lasts for 2-3 months, it is a phenomenon of hair loss if it loses more than 100 hair per day. At present, due to the increasing pressure of social life, more and more people have serious hair loss problems, how can we get rid of "hair loss anxiety" and keep the "overhead event"?
The Gospel of the Hair Loss Star:
Hair follicles regenerate and welcome new hope
Recently, a new study from Yale University in the United States has given hair loss patients the hope of "hair regeneration". In this study, the researchers took a unique approach to identifying the molecular signals that induce hair follicle formation, making hair follicle regeneration further possible. The results of the study were published on Dimension Cell under the title "Decomposing a deterministic path to mesenchymal niche formation by two intersecting morphogen gradients."
Figure 1 Research results (Source: Developmental Cell)
For decades, scientists have been unable to solve the problem of hair follicle regeneration. Because dermal aggregates (DCs), signal centers that induce hair follicle growth and differentiation, form too quickly to be visualized and captured. Dermal aggregates are clusters of cells located below the epidermis layer of the skin that acts as the central commander of follicle activity by sending signals to the outer layer of the skin indicating that it forms a hair follicle and determines the size of the follicle. Clarifying the steps of signal formation has been an important challenge for researchers because the process is difficult to track over time. The researchers say overcoming this obstacle could open the door to hair transplantation, test new hair loss drugs by replicating dermal aggregates, and generate hair follicles in a 3D culture model.
In this study, the researchers used mouse skin single-cell RNA sequencing data to design an algorithm that aligns a series of single-cell profile "snapshots" to reconstruct the development of dermal aggregates, thereby outlining the path of immature skin cells to maturity. What's more, researchers can use this method to investigate the molecular signals that act as engines in this process, and by combining the calculations with in vivo genetic experiments, they are able to identify key signals involved in dermal aggregate formation. This work is crucial for developing new hair regeneration methods that will help pave the way for follicle regeneration applications in adults. In addition, the findings show that the algorithm can be used to understand signals and cell behavior that were previously impossible to capture.
Development of technology for the treatment of hair loss
Scientists are always on the road
1. Stem cell therapy brings hope for the treatment of hair loss
The Dermatologic Surgery magazine published a study titled "The Effect of Conditioned Media From Human Adipocyte-Derived Mesenchymal Stem Cells on Androgenetic Alopecia After Nonablative Fractional Laser Treatment" (Figure 2) research paper showing that Fat-derived Mesenchymal Stem Cell Culture Solution (ADSC-CM) can significantly increase hair density and volume in patients with androgenic alopecia (AGA) [2].
Figure 2 Research results (Source: Dermatologic Surgery)
In the study, the researchers treated 30 patients treated with a non-ablative dot matrix laser treatment topically with ADSC-CM or placebo solution. The researchers measured trends in hair density by taking pictures that recorded the patient's hair density at each visit and compared it with clinical digital photographs to get an overall improvement score (GIS). Changes in hair density during treatment showed that the hair density of patients in the ADSC-CM group was significantly higher than that of the placebo group, and their GIS was also significantly higher than that of the placebo group. In addition, no associated adverse effects were found following adsc-CM application during the study[2].
This study shows that ADSC-CM has a significant effect in the treatment of AGA, and topical ADSC-CM treatment is an effective choice for AGA patients.
2. Regulatory T cells activate hair follicle stem cells and promote hair follicle regeneration
In 2017, researchers at the University of California, San Francisco, discovered a new mechanism of hair growth, that is, regulatory T cells in the skin can directly activate hair follicle stem cells, which in turn promotes hair follicle regeneration [3], and the relevant research results were published in Cell under the title of "Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation". Studies have shown that regulatory T cells play a vital role in the hair follicle regeneration process, and once the regulatory T cells in the skin are removed, the hairs no longer grow [3].
Figure 3 Research results (Source: Cell)
In the study, the researchers first temporarily removed regulatory T cells from the mouse skin and removed the mouse hair to observe the subsequent growth of the mouse hair. The results found that mice with removed regulatory T cells were unable to grow hair compared to the control group of mice. Next, the researchers tracked regulatory T cells in mouse skin at different stages of hair growth by fluorescent markers and found that most of the regulatory T cells in the resident skin were concentrated near the hair follicle and the number increased threefold before the hair follicle entered the regenerative phase. And, the researchers found that removing regulatory T cells from the skin within the first three days after shaving off the skin blocked hair regeneration. In general, hair follicle regeneration is activated within these three days, and once hair follicle regeneration is turned on, regulatory T cells are removed after three days, which has no effect on hair regeneration.
This study shows that regulatory T cells play an important role in the hair follicle regeneration process and will help better explore ways to treat hair loss.
Current mainstream treatment methods for hair loss:
Hair transplantation + medication relief
1. Hair transplantation
In 2020, China's hair loss population exceeded 250 million, while only 516,000 hair transplants were performed, with an penetration rate of 0.21%. The huge number of hair loss people coupled with the extremely low market penetration rate hints that China's hair medical service industry, represented by hair restoration, will become an outlet for explosive growth.
Hair transplantation surgery has developed so far, and has experienced an early practice period, a theoretical exploration period, a technical transition period, and a mature technology period. In 1995, American doctors Bernstein and Rassman first proposed the concept of "Follicle Unit Transplant" (FUT). In 1997, they again proposed that using a microscope to acquire follicular units could increase efficiency to 10 percent. Subsequently, FUT developed into a mature hair transplant surgery that swept the world.
Significant advantages over previous hair transplant surgeries include the following:
Hair follicle isolation and planting can be carried out in full accordance with the natural condition of the hair follicle unit;
Using a microscope to isolate hair follicles can reduce follicle damage by 30%-50% compared to eyelid isolation;
The survival rate of hair follicle transplantation is much higher than that of traditional hair transplant surgery [4].
At the same time, FUT also has certain defects, mainly including:
Requires a strong surgical team and excellent surgical procedures;
It takes a long time to complete scalp incision and scalp strip separation;
The flap must be extracted from the posterior occipital region, which can easily cause wounds, leave scars, and scars that cannot be completely removed [4].
In 2002, Dr. Rassman proposed "Follicular Unit Extraction" (FUE). Its advantages are: no surgery, small wounds, low pain, fast healing, and a good appearance after surgery; the scope of transplant extraction is relatively large, and even hair follicles can be extracted from the beard area.
FUT and FUE are currently internationally recognized as mature hair transplant surgeries.
2. Relieve hair loss with medications
★JAMA study: The treatment of hair loss in men is most effective at 0.5 mg of tasteride taken orally daily
In February, a meta-study published in JAMA Dermatology summarized 23 studies revealing the effects of three oral and topical medications (minoxidil, dutasteride and finasteride) in different doses for 2 to 4 months on thinning men's hair, titled "Relative Efficacy of Minoxidil and the 5-α Reductase Inhibitors in." Androgenetic Alopecia Treatment of Male Patients: A Network Meta-analysis" (Figure 4).
Figure 4 Research results (Source: JAMA Dermatology)
In the study, researchers counted the total number of hairs and hair growth of patients after 24 weeks of treatment and 48 weeks of treatment to measure the effectiveness of treatment. The results showed that 0.5 mg of tasteride was most effective daily, followed by oral 0.5 mg/day finasteride, 0.5 mg/d minoxidil, 1 mg/day finasteride, 5 percent topical minoxidil, 2 percent topical minoxidil, and 0.25 mg/d minoxidil [5].
★ FOL-005 concerned about female hair loss
In the context of hair loss products focusing more on men, the Swedish company Follicum has actively developed a product for the treatment of female hair loss FOL-005. FOL-005 is a synthetic peptide based on the human protein osteopontin (associated with hair growth) and is considered the most likely to be a strong competitor to minoxidil and finasteride.
In 2018, in a clinical study confirming the safety of FOL-005, the findings showed that after receiving FOL-005 treatment, patients had an average increase of 7 hairs per square centimeter on their scalp, a statistically significant increase in hair compared to baseline. And, subjects treated with the highest dose of FOL-005 significantly increased the number of hair follicles by 11%. In addition, the ratio of the amount of hair during the growth period to the dormant period increased by 18%, while the corresponding amount of placebo was negative 16%. All of these results indicate that FOL-005 is a promising hair loss product.
★ "The Hope of a Hair Loss Star" – JAK inhibitors
JAK-mediated signaling pathways include jak-STAT pathway, MAPK pathway, and P13k-AKT pathway, where many cytokines involved in the pathogenesis of alopecia areata rely on JAK-STAT signaling, so JAK-STAT is considered an attractive signaling pathway in the treatment of alopecia areata [6], and JAK inhibitors are also considered to be an effective treatment for alopecia areata. At present, the JAK inhibitors approved in the United States include rucortinib for the treatment of blood diseases and tofacitinib, barritinib, uppatinib and so on for the treatment of rheumatoid arthritis.
Among them, baretinib has the most potential to become the first FDA-approved alopecia areata therapy. Barritinib is an oral JAK inhibitor that inhibits all JAK enzymes, especially JAK1, JAK2, and TYK2. In one clinical trial, patients treated with 4 mg of barritinib experienced significant improvement in hair growth at 24 weeks of treatment. The hair coverage rate of 28.2% of patients in the barretinib group exceeded 80%, while only 1.3% of patients in the control group had hair coverage of more than 80%, and the average hair coverage rate of these patients before receiving hair loss treatment was only 14.5%.
Hair loss is a "worldwide problem" that needs to be solved urgently, and many scientists are sparing no effort to find an effective solution. Nowadays, thanks to the advancement of hair transplantation technology and the development of symptomatic drugs, we can already treat hair loss to a certain extent. I hope that there will be more relevant studies in the future, which can effectively help you with hair loss problems.
Source: YouTube, for academic communication only.
Written by | Muzijiu
Typography | Muzijiu
End
Resources:
[1] Qu R, Gupta K, Dong D, et al. Decomposing a deterministic pathto mesenchymal niche formation by two intersecting morphogen gradients. DevCell. 2022 Apr 6:S1534-5807(22)00205-2. doi: 10.1016/j.devcel.2022.03.011. Epub ahead of print. PMID: 35421372.
[2] Lee YI, Kim J, Kim J, et al. The Effect of Conditioned Media From Human Adipocyte-Derived Mesenchymal Stem Cells on Androgenetic Alopecia After Nonablative Fractional Laser Treatment. Dermatol Surg. 2020Dec;46(12):1698-1704. doi: 10.1097/DSS.0000000000002518. PMID: 32769526.
[3] Ali N, Zirak B, Rodriguez RS, et al. Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation. Cell. 2017 Jun1;169(6):1119-1129.e11. doi: 10.1016/j.cell.2017.05.002. Epub 2017 May 25.PMID: 28552347; PMCID: PMC5504703.
[5] Gupta AK, Venkataraman M, Talukder M, et al. Relative Efficacy of Minoxidil and the 5-α Reductase Inhibitors in Androgenetic Alopecia Treatment of Male Patients: A Network Meta-analysis. JAMA Dermatol. 2022 Mar1;158(3):266-274. doi: 10.1001/jamadermatol.2021.5743. PMID: 35107565; PMCID:PMC8811710.
This article is a biological exploration original, welcome to forward and share. If any other media or website needs to be reprinted, the source of biological exploration must be indicated in front of the main text.
![Stanford scholars have used genetic engineering to grow hair follicle cells that have grown human hair on hairless mice[fig]](data:image/gif;base64,R0lGODlhAQABAIAAAP///wAAACwAAAAAAQABAAACAkQBADs=)