For those who have never had to deal with hair loss, having a healthy head of hair is often taken for granted. Although it has been found that up to 100 hairs on average lost in a day is normal, any amount above that threshold can eventually lead to hair thinning and loss. The International Society of Hair Restoration Surgery reports that about 35 million American males and 21 million American females suffer from hair loss.
Our hair is one of the most prominent external indicators of youth, health, and a central part of an individual’s visual identity. For many, losing hair is akin to losing an integral part of themselves.
The global market for Alopecia treatment was valued at over 8 billion USD in 2023. The loss of hair can be hugely detrimental to mental health and self-esteem; in some individuals this thinning and gradual falling out of hair can occur as early as in their twenties. In spite of its common occurrence, those experiencing hereditary hair loss can face psychological stress and disturbance, ranging from feelings of embarrassment to jealousy. A full head of hair is an important social and psychological indicator of wellness. Evidently, our hair is vital to who we are–what can we do to understand and treat hair loss?
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As hair follicle diameter decreases, effects can also be seen on the scalp and nearby sebaceous glands. Additionally, graying hair can be attributed to the loss of pigment cells. In general, with age, hair follicles lose their regenerative potential. The hair follicle is such an incredible cell resource–one of the only organs in the human body that exhibits cyclic growth and loss–preserving these cells before they become senescent can be a key differentiating factor in their future usability. A phenomenon known as senescent alopecia also occurs with age. Studies have shown that with age, the anagen phase of the cycle becomes shorter, and miniaturization of the follicle occurs. Although there is debate as to the direct cause of senescent alopecia, it is found that with age, hair follicle cells become senescent, and the follicles become smaller and thinner.
With age, HFSC (Hair Follicle Stem Cell) activity decreases. The activity of these stem cells within the hair follicle niche is fundamental to maintaining hair growth cycles and homeostasis. Graying hair, decreased hair production, and the thinner of follicles are often associated with stem cell aging. Decline in HFSC activity drastically decreases the regenerative capacity of hair follicles.
These cells serve in key signaling pathways that control hair growth and hair health. Thus, seeking solutions that preserve SCs in their youthful state is integral as an insurance policy against the biological aging of our cells.
Androgenetic Alopecia is the most common form of hair loss, affecting up to 50% of the male population by age 50. Women can also experience this, particularly evident in thinning and hair loss at the crown of the scalp. This form of hair loss is influenced by genetics and hormonal changes.
Androgens (growth and reproductive hormone), particularly in the form DHT, play a crucial role in regulating hair growth. Overexpression of such hormones shorten the growth phase of hair and cause them to miniaturize, leading to thinner and shorter strands. Follicular miniaturization is a process where hair follicles gradually become smaller and produce thinner, shorter, and less pigmented hair over time.
Eventually, these affected follicles stop producing new hairs altogether, leading to thinning hair and baldness. The genetic predisposition to androgenetic alopecia means that the condition runs in families, and the likelihood of developing it increases if one or both parents are affected. While the condition is commonly associated with men, it can affect women.
Telogen effluvium (TE) is a form of hair loss that typically occurs after stress, hormone changes, or medications. It's characterized by the excessive shedding of hair, where more hairs than usual enter the telogen (resting) phase of the hair growth cycle and subsequently fall out. Up to 70% of anagen (growth phase) hairs can transition into the telogen phase and cause excessive hair loss. By contrast, in a healthy scalp, around 85% of hairs are in anagen and 15% are in telogen at most given times. Unlike androgenetic alopecia, which can lead to permanent hair loss and balding patterns, telogen effluvium involves a diffuse thinning of hair across the scalp without necessarily leading to complete permanent baldness.
Common triggers to TE include severe infection, major surgery, post-partum hormone changes, decrease in estrogen, low protein intake, hyperthyroidism, and iron deficiency. TE is also associated with certain medications, such as beta blockers, retinoids, excess vitamin A, carbamazepine, and immunizations.
Alopecia Areata is an autoimmune disease in which the body attacks its own hair follicles and causes fallout and inflammation in the area. Hair typically begins to fall out in patches around the scalp. However, this attack does not completely destroy hair follicles, so they do grow back, but in patches and often thinner or grey. AA can affect any population group–onsets of the condition commonly begin in teens and people in their twenties and thirties.
A number of factors can cause AA. Certain inherited genes place people at risk, so those with close relatives who have AA are at higher risk. Additionally, those with other autoimmune conditions such as psoriasis, vitiligo, or atopic dermatitis are at an increased risk of developing it. Certain studies have also linked long-term cigarette use to an increased risk of developing the condition.
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Stem cell therapies for hair follicle regeneration have been extensively studied; currently, there are over 4700 NIH-sponsored clinical trials to understand the pathways and applications of stem cell therapy. The hair follicle (HF) is a regenerative organ housing various stem cell groups, including HF stem cells in the bulge area and dermal papilla (DP) cells. Consequently, cell-based therapeutic research has identified new strategies in treating conditions like androgenetic alopecia and alopecia areata.
One widely studied method for follicle regeneration injects stem cells directly into the scalp for growth. Stem cells from the follicle bulge are centrifuged and isolated, then directly injected along with newly generated follicles to stimulate new follicle growth in bald patches of the scalp. The follicle contains a wealth of different stem cell types and thus is a valuable cell source for regeneration. Other treatments may use MSCs (mesenchymal stem cells), isolated either from adipose tissue or the hair follicle itself.
Another approach uses paracrine signaling (cell-to-cell signaling) to stimulate hair follicle stem cells and drive hair growth. In hair loss, hair stem cells remain but often in a senescent state. Studies have suggested that follicle aging can be attributed to stem cell exhaustion, so activation of certain pathways within the follicle via growth factors, peptides, or select genes can activate stem cells back to a youthful state and drive growth.
PRP, or Platelet-rich-plasma, consists of two elements: plasma, the liquid portion of blood, and platelets, wound-healing blood cells. Platelets are known for their clotting mechanisms and ability to trigger cell migration and cell regeneration at wound sites. PRP is also rich in growth factors, which can stimulate hair growth and cell rejuvenation. The procedure consists of taking a sample of the patient’s own blood, and spinning the sample in a centrifuge to separate out PRP from the rest.
PRP, when applied directly after microneedling or laser to the scalp, has shown potential to stimulate new hair growth and prevent further hair loss from happening.
Extracellular vesicles (EVs), otherwise known as exosomes are emerging as a promising new approach to cell-based therapies. Often collected from a proliferated cell population, the secretome (complete set of molecules secreted by cells) can be used in a wide variety of regenerative therapies from wound healing, sport medicine, to aesthetic applications.
Exosomes are responsible for extracellular signaling and intracellular shuttling; they are the delivery vehicles between our cells. They can contain and deliver key cellular elements like growth factors, proteins, and matrix molecules while also providing genomic components like DNA, RNA and MicroRNA.
Studies show that these cell-free elements, like exosomes and growth factors, derived from a person's own stem cells hold significant therapeutic potential, helping support cell migration, proliferation, and regeneration.
Some skin conditions currently being researched alongside EVs/Exosomes include wound healing, scarring, burn healing, psoriasis.
Researchers at Yokohama National University successfully generated hair follicles in cultures. Taking it one step further from hair transplant surgeries, hair cloning takes cells from the healthy hair follicle, replicates them in a laboratory, and implants the cloned cells into the scalp. The hope is that these cells will generate new hair follicles, leading to new hair growth. This method could potentially provide an unlimited source of new hair for individuals experiencing hair loss. However, this therapy is still in research and needs further development and data to be commercially available.
Minoxidil (Rogain): Often sold under the brand name , Monoxidil is an over-the-counter topical treatment applied to the scalp, which can stimulate hair growth and slow the progression of hair loss in both men and women. It needs to be applied continuously, as stopping treatment can lead to resumed hair loss.
Finasteride (Propecia, Proscar): A prescription oral medication for men that inhibits the production of dihydrotestosterone (DHT), the androgen hormone implicated in AGA. It can slow hair loss and even lead to regrowth in some cases.
Dutasteride: Similar to finasteride, this medication is also a DHT inhibitor but is not FDA-approved for hair loss treatment. Some doctors may prescribe it off-label for AGA.
Hair transplant involves moving hair follicles from a part of the body (usually the back of the head) to the balding or thinning areas. Techniques such as follicular unit transplantation (FUT) and follicular unit extraction (FUE) can yield natural-looking results. However, surgery can be expensive and involves recovery time.
LLLT devices, including laser combs and helmets, use red light therapy to stimulate hair growth. The effectiveness can vary, and they are typically used as an adjunct to other treatments.
Involves creating controlled wounds to the scalp via tiny punctures. Microneedling has been widely studied and shown to stimulate blood and repair activity in the scalp area. It also demonstrates potential for better absorption of vitamins, serums, and other treatments beyond the skin barrier. Often, microneedling is paired with other products such as Minoxidil or PRP (platelet-rich plasma).
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