Hair Cloning

Introduction

What if we could produce hair through the use of cloning? The treatments on the market today focus on maintaining what hair you have left or moving the small amount of permanent hair to regions where hair has been lost. Through the harnessing of tissue cloning we may soon be able to grow fresh new hair.

Cloning techniques involves the propagation of cells for therapeutic use. Human stem cells possess the unique ability to differentiate into various cell types. In injury or disease an organ may be damaged and unable to heal. By administering primed stem cells to the injured area the cells can settle in to the tissue and begin repairing or replacing the damaged tissue. This is much easier said than done!

Stem cells with the ability to differentiate into ANY cell type are extremely limited and are most abundantly found in developing embryos which makes generating them and obtaining them difficult. Stem cell contained within various tissues are already partially committed to a cell type and can function just as well in repairing the damaged their specific tissue type.

For hair, the specific stem cell is the dermal papilla cell that resides in the hair follicle. The dermal papilla cells of the healthy, long-lived, follicles do not appear to migrate from their healthy follicles to the miniaturizing follicles of the crown and hair line, and if they did migrate then the follicle left behind may become miniaturized and unable to robustly produce hair.

Method

HairClone© is developing a technique where they harvest roughly 50 hair follicles from the permanent regions of the scalp through FUE harvest. FUE harvest results in very minimal scarring and 50 extractions are undetectable (Figure 1). Those follicles are then either stored for a later time when the patient is ready for a transplant or immediately cultured. The dermal papilla cells are cultured and propagated using advanced tissue culture techniques that maintain their potency as hair producing cells while also producing large numbers. It is this point where the balance between the ability to generate large numbers of potent cells that a breakthrough is required. Often, cells that replicate happily in tissue culture lose their characteristics as stem cells and become attenuated to grow in their new out of body environment. If the researchers at HairClone© are successful, they will be able to generate an almost limitless supply of hair growing stem cells.

Hair cloning process

Hair cloning process

Once the cells are propagated, they are injected into the balding scalp of the donor patient. Hypothetically, the cells will migrate to the miniaturized follicles in the balding region or begin the formation of novel hair follicles. The growth of the hair in the balding regions is then monitored to determine if further treatments are necessary.
Won’t the new hair fall out just like the other hair in the area? At this point it is not known if the new hair is “permanent”, >50 year, or >20 year. It is hypothesized that since the source of the stem cells is from the permanent hair of the back of the head, the newly formed follicles will be resistant to the factors that contribute to androgenetic alopecia.

We are excited to see if this technology will develop into a treatment that we could someday offer to our patients as an effective treatment for hair loss.

The Basics of Hair

Introduction

Hair and hair restoration terminology can be confusing on the surface. This article will better acquaint you with the details of hair and language that is used by professionals. Reviewing this article should help you better understand the advice and descriptions provided by your hair restoration surgeon as well as prepare you for asking questions so that you get the most accurate information. We at Seager want you to feel informed and comfortable throughout the entire process of hair restoration.
In this article we will go over follicle anatomy and the role of different parts of the follicle. Next we will discuss how hair grows and what that means for baldness. We will next talk about the characteristics of hair and how it is pigmented and why hair maintains a curl. Hair density and the permanence of hair will be discussed and finally common hair disorders.

The hair follicle

Each hair follicle is considered a mini organ with different components that each possesses a distinct function (Figure 1). The root sheath of the follicle is a specialized layer of cells that house the hair bulb and growing hair fibre. The hair fibre is what you see protruding from the scalp and it is composed of three distinct cell types all of which are dead by the time the hair fibre grows out of the root sheath. The hair bulb contains the dividing cells that grow into the hair fibre. Along the length of the root sheath we find a small anchoring muscle, the arrector pili, which is responsible for making the hair stand up in response to emotional stimuli (e.g., fear or surprise) or physical stimuli (e.g., chill). Also attached to the root sheath is the sebaceous gland which is responsible for coating the hair with sebum. Sebum is necessary to prevent the hair fibre from becoming too dry as well as lubricating it as it emerges from the hair follicle.

The anatomy of the hair follicle

The Hair Follicle is a mini organ consisting of many parts.

 

Follicular units

If we observe from the level of the scalp we see that hairs appear to protrude from the scalp in irregular groups. It turns out that follicles tend to arrange in groups of 1-4 resulting in what are called follicular units. Follicular units share usually the same pore or pores very close together. In rare instances up to 7 hairs have been observed in single follicular units. The hair follicles of the body do not tend to group together to such a high number with 2 being the typical maximum count.
The distribution of the follicular unit density is not uniform throughout the scalp. Hair restoration surgeons have observed that 1-2 hair containing follicular units are normally found at the hair line with higher density follicular units (i.e., >3 hairs per follicular unit) found in the mid scalp and vertex (i.e., the crown) (Figure 2). The distribution of follicular units of different densities contributes to the natural fullness of scalp hair and the softness of the hair line. Natural looking hair line restoration requires the placement of single hairs followed by greater density implantation to prevent an artificial “too dense” hair line that can be produce by in-experienced practitioners. Hair restorations surgeons take immense care to study the density of a patient’s hair to plan the appropriate hair line so that a natural-looking hair is restored.

Hair follicle groupings

Hair Follicles can be in groups of 1-3, with rare instances of 4 or 5!

Hair growth cycle

Human hair grows asynchronously which is to say that it does not grow and shed all at once. Most other mammals have synchronous hair growth to accommodate changes in season. The random distribution of hair, in various points of the hair growth cycle, ensures that there are always 85% of our available follicles containing hair (1). Any given follicle can grow hair for between 3-10 years, with this number varying between people. With hair growing about 1.3 cm per month (2), human hair reaches an average maximum length of 101 cm. Some people’s hair grows faster but for less time and some people’s hair grows slowly for a longer time.
The hair cycle is described by 4 distinct steps; anagen, catagen, early telogen, and late telogen. Anagen is the growth part of the cycle and lasts roughly 6 years. Anagen is followed by the brief catagen phase, where the follicle stops producing additional hair. In early telogen, the follicle prepares to shed the hair. The final step of the hair growth cycle is the late telogen where the follicle rests.

The hair growth cycle

Hair follicles produce hair by growing through a cycle.

Chemical communication occurs between the hair follicle and the nearby fat layer of the skin, which appears to play a crucial role in perpetuating the hair cycle. Maintaining or reinitiating this communication, is the subject of intense research. Platelet-rich plasma (PRP) (3) and transplantation of fat-derived stem cells (4) aim to coax the hair follicle back into the anagen step of the hair cycle.

Hair fibre and curl

The hair fibre is composed of three layers; the outermost cuticle, the cortex, and the innermost medulla (5) (Figure 4A). The cuticle is the protective layer that surrounds the inner cells of the hair. The cuticle itself does not have any colour. The bulk of the hair fibre is made up of the cortex cells that provide the structure of the hair by contain large amounts of the protein keratin. The cortex cells also contain the pigment that imparts colour to the hair fibre. The function of the medulla is bot well understood.
The curl of hair is created by the shape of the follicle beneath the skin (6,7). A curved follicle produces a curled hair fibre. As the hair bulb produces cortex cells, they fill up all of the space of the root sheath. The cells at the outside of the curve tend to be longer while the cells at the inside of the curve tend to be shorter. The shape is made permanent once the cortex cells die as the hair fibre emerges from the follicle. The shape of the exit of the pore also has been implicated in the hair curl. A more round pore exit is associated with straight hair, while an elliptical pore exit is associated with curly hair.
Modification to the curl of hair can be induced by heat, humidity, or chemicals. Heating of the hair fibre with blow dryers or hair irons cause changes to hydrogen bonds within the keratin of the cortex cells. Throughout the day the hair continuously absorbs humidity from the environment which reverses the hydrogen bond breakage.

Anatomy of the hair fibre

The structure of hair is made up of three distinct layers. The cortext contains two a ratio of two distinct pigments that result in the colour of the hair.

Permanent hair straightening or curling is performed with chemicals that are able to break the disulfide bonds of the hair fibre. The disulfide bonds of hair are much stronger than the hydrogen bonds that can be simply heat treated. The chemical agents used in permanent straining or curling are very harsh and may damage the scalp is incorrectly handled.

Hair colour

Human hair colour is the product of a ratio of two melanin molecules; eumelanin and pheomelanin (8) (Figure 4B). All of the ranges of hair colour from blonde, red, brown, to black are created by the ratio of eumelanin and pheomelanin. As one ages the cells responsible for making the pigment become less effective and produce less pigment resulting in grey or white hair.
Hair may be coloured artificially with different levels of permanence. The cuticle of the hair fibre prevents environmental chemicals from entering into the hair but it also possesses properties that we can harness for artificial colouring. Temporary hair dye is designed to bind to the cuticle and is typically composed of large pigments molecules. Due to the loose association of the large pigment molecules with cuticle, they can easily be washed out. Semi-permanent hair dye functions like temporary dye, in that is able to interact with the rough texture of the cuticle but is instead composed of small pigment molecules that are more difficult to wash out of the rough cuticle. Permanent hair dye requires a different approach where the pigment molecules absorb into the cortex of the hair fibre where it cannot be washed out easily. To allow passage of the dye into the cortex of the hair fibre the hair is made to swell by applying an oxidizing agent and an alkaline agent.

Hair density and hair caliber

Humans possess roughly 100 000 hair follicles throughout the body and 20 000 of those are located on scalp. The appearance of a dense head of hair is the sum of multiple aspects of hair. The scalp of average person has roughly 80 follicular units/cm2 (5).
The apparent density is the result of the relationship of hair growing out of the scalp. Follicle units that contain greater numbers of hairs (e.g., 3-4 hairs) tend to impart greater density. The density of hair is highest at the top of the head and at the crown. The density of the hair at the hairline is considerably less with many follicular units containing only one or two hairs. Hair restoration surgeons take this fact into account, reserving 1 and 2 hair grafts for the hairline and greater hair grafts for space filling.
Hair caliber describes the relationship between the number of hair and hair diameter. Thick hair fibres have a thickness of 90-100 μm, medium hair has a thickness of 50-80 μm, and thin hair has a thickness of 30-40 μm. When determining hair caliper we take into account both the hair thickness and follicular density. A person with 50 units/cm2 and a thickness of 100 μm has roughly double the hair mass of a person with 85 units/cm2 with a hair thickness of 30 μm.
In male and female pattern baldness hair density is lost through the follicles miniaturizing and converting to produce vellus hairs. Vellus hairs are different from the thick pigmented terminal hair of the scalp because they do not contain pigment, are thin, and only grow a few centimeters.

Permanent and non-permanent hair

Not all of the hair of the scalp is vulnerable to male or female pattern baldness. Hair restoration surgeons have observed innumerable cases of hair loss and have determined the regions of the scalp where hair is deemed permanent. Specifically this is hair on the back of the head between the middle of the neck. The permanent region continues in a band from this region to over the ears and onto the temples. Any harvesting of hair grafts occurs from these permanent regions as any harvesting performed outside of these regions may end up falling out as male pattern baldness progresses.

Hair disorders

Androgenetic alopecia

Androgenetic alopecia is the medical name for the common age related hair loss that affects both men and women. Treatment for the condition can be performed pharmaceutically through the administration of topical minoxidil for men and women or oral finasteride for men. Finasteride is only indicated for use in men due to complications that could arise should pregnancy occur. Androgenetic alopecia presents in different ways in men and women. Men experience a distinct pattern called male pattern baldness where the hairline recedes accompanied a thinning of the crown. Female pattern baldness presents as diffuse thinning of the hair.

Alopecia areata

Alopecia areata is a rare auto-immune disease that causes patchy hair loss. Alopecia areata is treated with immune modulatory pharmaceuticals and corticosteroids (1,9). Alopecia areata affects men and women equally and can vary dramatically in severity. Alopecia totalis is a form of alopecia areata that affects the entire scalp. Alopecia universalis is the more severe form of alopecia where then entire body does not have hair. Alopecia areata can in some patients be permanent but is often temporary or cyclical. Individuals with alopecia areata may be eligible for a hair transplant if a region of hair loss has been stable without further hair loss for one year.

Conclusion

This review hopes to give you the basics of hair biology and inform you of aspects of hair anatomy that are relevant in how you hair restoration surgeon makes decisions about your treatment.

References

1. Unger WP, Shapiro R, Unger R, Unger M, editors. Hair Transplantation. 5th ed. Informa Healthcare; 2011. 538 p.
2. How hair grows [Internet]. American Academy of Dermatology, Inc; 2018 [cited 2019 Mar 19]. Available from: https://www.aad.org/public/kids/hair/how-hair-grows
3. Alves R, Grimalt R. A Review of Platelet-Rich Plasma: History, Biology, Mechanism of Action, and Classification. Skin Appendage Disord. 2018 Jan;4(1):18–24.
4. Guerrero-Juarez CF, Plikus MV. Emerging nonmetabolic functions of skin fat. Nat Rev Endocrinol. 2018 Mar;14(3):163–73.
5. Lam SL. Hair Transplant 360. Vol. 1. Jaypee Brothers Medical Publishers (P) LTD; 2011.
6. Tirado-Lee L. The Science of Curls [Internet]. Helix Magazine; 2014 [cited 2019 Mar 19]. Available from: https://helix.northwestern.edu/blog/2014/05/science-curls
7. Plowman JE, Harland DP, Deb-Choudhury S, editors. The Hair Fibre: Proteins, Structure and Development. Springer Nature Singapore Pte Ltd.; 2018. 224 p. (Advances in experimental medicine and Biology; vol. 1054).
8. Ito T. Recent advances in the pathogenesis of autoimmune hair loss disease alopecia areata. Clin Dev Immunol. 2013;2013:348546.
9. AAD. Alopecia areata: Diagnosis and Treatment [Internet]. American Academy of Dermatology, Inc; 2018 [cited 2019 Mar 22]. Available from: https://www.aad.org/public/diseases/hair-and-scalp-problems/alopecia-areata#treatment

Pioneers of hair transplantation in Toronto

HISTORY

The first record of a successful hair transplant was in 1822, when a German medical student named Diffenbach performed an experimental surgery on himself and his mentor Dr. Dom Unger, they used hair from one area of a patient’s scalp and transported it to another area1.

The first modern surgical technique was described in 1939 by a Japanese dermatologist named Dr. Shoji Okuda. Dr. Okuda published what became known as “The Okuda Papers” in the Japanese Journal of Dermatology and Urology, describing his technique, full-thickness grafts of hair-bearing skin from hair-bearing areas to hairless areas to correct hair loss on the scalp, eyebrows and upper lip. These papers did not gain notoriety until 2003 when Dr Yoshihiro Imagawa was able to translate them for English speaking audiences post World War II2. In 1952 an American Dermatologist named Dr Norman Orentirech performed the first modern-day hair transplant in New York3. Dr. Orentreich was able to publish his work in 1959 in the Annals of the New York Academy of Science and it is this work that underlies all modern hair restoration endeavours. The paper presented the concept of “donor dominance” and “recipient dominance” for the first time. This was significant as the donor dominance concept explained the contradictory results of many previous hair transplantation studies.

Nonetheless, it wasn’t until mid-1990 that surgical hair restoration came out of the dark ages to yield actual ‘natural hair’ resembling results. This is due to the introduction of follicular unit micrografting or follicular unit transplantation (FUT). This has made follicular unit extraction hair transplantation a virtually undetectable, practical option for many hair loss sufferers.

TORONTO HAIR TRANSPLANT PIONEERS

Toronto, Ontario, in particular, has seen its fair share of pioneering hair transplant surgeons. One of the first is Dr Walter P. Unger. Dr Unger is a clinical professor of Dermatology and Director of the Dermatologic Surgery Fellowship Program at Mt. Sinai School of Medicine in New York, as well as a Director of the Fellowship Program for the International Society of Hair Restoration Surgery. He is an associate professor (Dermatology) at the University of Toronto. He was the adjunct professor (Dermatology) at Johns Hopkins School of Medicine in Baltimore, Maryland from 2003 to 2007. He has private practices in Toronto and New York City4.

Dr Unger advanced Dr Orentreich’s principle of “donor dominance” in 1994 by helping shape surgeons’ understanding of the limitations of the donor area from which hair follicles are harvested. He was the first surgeon to define the parameters of what he defined as the “Donor Zone”, the zone from which the most permanent hair follicles can be extracted for transplantation. We know that transplanted hair will only last in its new site for as long as it would have lasted in the original one. These findings from Dr Unger continue to serve as the groundwork for hair follicle harvesting on which both FUT and follicular unit extraction (FUE) are based.

 

In 1995, Dr Unger was presented a Golden Follicle award for clinical expertise from the International Society of Hair Restoration Surgery (ISHRS)5. In October 2003, Dr Unger also won the Pioneer in Education Award-Hair Restoration from the ISHRS5. In 2007 and 2001 he won the Teacher-of-the-Year, Department of Dermatology, Mt. Sinai Medical School, New York and is considered one of Castle Connolly’s “Top Doctors” in New York Metro Area starting from 2007 to the present.

Dr Mark Unger is another independent practitioner of hair restoration surgery. He was a co-editor for Hair Transplantation, 5th Ed., the reference textbook in the field of hair transplantation. He is also a fellow of the International Society of Hair Restoration Surgeons. Additionally, he authored chapters on Hair Transplantation in major cosmetic surgery and dermatology textbooks. He also practices hair transplants in Toronto, Canada.

Dr. David J. Seager, is one of the true pioneers of Toronto hair transplants, his reputation as a truly innovative hair transplant pioneer is well known within the hair restoration world. He was the first to perform high density “one pass” sessions in the mid to late 1990s. The high-density sessions means an excess of 3,000 grafts at a time. Dr. Seager and his staff also pioneered what would become known within the hair transplant community as “Ultra Refined Follicular Unit Hair Transplantation”. So the Dr. Seager signature hair transplant was 3,000 graft densely packed “One area – One session”, then the Follicular Unit Micrograft Hair Transplant procedure was turned into a team effort, so the grafts were immediately placed into the incision after the tiny needle incision was made6. This technique is referred to as “stick and place” technique. This technique is ideal as it enables the staff to use smaller and less invasive needles for the incisions. It is easier to place a small graft into a small incision if it is a fresh incision. In October of 2001, Dr. Seager was honoured with the Golden Follicle Award by the ISHRS in recognition for his many clinical contributions to the field of hair transplantation5. Additionally, other well-known hair transplant surgeons from around the world have chosen to travel to Toronto to have Dr. Seager perform their own personal hair transplant procedures. Dr. Seager passed away in December 2006.

The City of Toronto for a Hair Transplant

Toronto, Ontario is a good city to choose to undergo a hair transplant. There clearly is a strong history of pioneers in the hair transplant industry and hair transplant doctors are well experienced. If you are planning on coming into the city from out of town, hotels and amenities are close and affordable. Additionally, welcoming over 40 million visitors annually, Toronto is the leading tourism destination in Canada7. Toronto is a bold, dynamic city that offers excellent attractions, music and events backed by the best convention and sports facilities in Canada.

Visit The Seager Hair Transplant Centre in Toronto

REFERENCES

  1. Historical Overview: 181 Years of Hair Restoration Surgery [Internet]. [cited 2018 Jan 29]. Available from: https://www.ishrs.org/mediacenter/media-history.htm
  2. Jimenez F, Shiell RC. The Okuda Papers: an extraordinary – but unfortunately unrecognized – piece of work that could have changed the history of hair transplantation. Exp Dermatol. 2015;24:185–6.
  3. The father of Hair Restoration. Dr. Norman Orentreich, 1953.| New Orleans, LA [Internet]. Hair Transplant & Hair Restoration Ctr | New Orleans, LA. 2016 [cited 2018 Jan 30]. Available from: https://gulfcoasthairrestoration.com/the-father-of-hair-restoration-dr-norman-orentreich-1953/
  4. Toronto 5 Burton Rd, Maps OCP-9393 S map: G. Walter P. Unger, MD | Hair Loss Doctor Toronto | ISHRS [Internet]. [cited 2018 Jan 29]. Available from: https://www.ishrs.org/users/wung
  5. ISHRS Past Award Winners | International Society of Hair Restoration Surgery [Internet]. [cited 2018 Jan 30]. Available from: https://www.ishrs.org/members-only/ishrs-past-award-winners
  6. Dr. David Seager has passed away but his legacy remains. | Regrow Hair Q&A [Internet]. [cited 2018 Jan 30]. Available from: https://www.regrowhair.com/hair-restoration-physicians/seager/
  7. Tourism [Internet]. City of Toronto. 2017 [cited 2018 Jan 30]. Available from: https://www.toronto.ca/business-economy/industry-sector-support/tourism/