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Dedication

DEDICATED TO: MEN AND WOMEN WHO SUFFER FROM HAIR LOSS

Table of Contents Introduction


BREAKING NEWS: BALDNESS REPORT

Chapter I
HOW IT WORKS: THE SCIENCE BEHIND STOPPING HAIR LOSS AND RE-GROWING HAIR WITH GROWTH FACTORS

Chapter II
NEW HAIR SCIENCE DISCOVERIES RELATING TO HAIR GROWTH

Chapter III
THE BASIS FOR DHT AND 5 ALPHA REDUCTASE INHIBITORS

Chapter IV
RESEARCH ARTICLES

Chapter V
STEM CELL INJECTION vs GROWTH FACTORS FOR HAIR LOSS

Chapter VI
MECHANICAL DEVICES AND HAIR FOLLICLE HEALTH

Chapter VII
VITAMINS, MINERALS, HERBS and ORGANIC INGREDIENTS IN HAIR FOLLICLE HEALTH

Conclusion: FACT: CURRENTTREATMENTMETHODSHAVEPROVENUNSATISFACTORYTO MANYHAIRLOSSSUFFERERS.

EXISTINGSOLUTIONSAREEITHERINCOMPLETEORTHEYOFFERONLYAPORTIONOF THEDESIREDOUTCOMES.

DEDICATION
THIS BOOK IS DEDICATED TO: Men and Women who suffer from Hair Loss This Book is dedicated to all males and females throughout the world who are suffering from hair loss. The authors recognize that a lifetime of searching for a legitimate and validated solution to hair loss by so many millions has resulted in disappointment after disappointment. Well meaning Informative web sites are dedicated to informing the public of the latest advances in solving this age old problem. They include informing the public of all types of compounds of vitamins, herbs, minerals, natural and organic food substances, plant substances and too many others to mention here. These marketed products are both topically applied and ingested orally. There are electromechanical devices, cold low-level light lasers, vibrators, vascular stimulating heating instruments, special combs and brushes, massagers, lamps, electrical stimulators and other proposed cures that again are too numerous to mention. In addition: the injection of serums and stem cells, surgical procedures, and biomedical solutions both accepted and experimental are being advanced. More variations of the above remedies are advanced daily and it is impossible for anyone to personally evaluate all of the options that are available today. As clinicians that have treated over 20,000 patients collectively in offices throughout the State of California, and as researchers we find evidence to validate some of these hair stimulating approaches. Yet, so many of these approaches simply cannot and do not work due to the bodys own physiological and anatomical mechanisms of protection. The bodys own skin is designed to not permit passage of foreign substances including viruses and bacteria in order to prevent infections and other harmful reactions. That being said, with new technological breakthroughs in molecular transport, the smaller proteins could be made to ingest into the circulatory system and subsequently into the cell membrane. However, large molecular structures over 500,000 daltons probably cannot penetrate the stratum to the depth required to enhance cell function. Compounds of less than 50 amino acids appear to pass through the cell wall into the nucleus while those larger than 500,000 daltons or 50 amino acids do not. The fact remains that the problem of hair loss persists. This suggests that the illusive solution that is sough in personal hair growth evades many. This book, therefore, is written to be an objective guide for the reader in the hopes of aiding him in his evaluation of the various available remedies to slow or stop hair loss and perhaps even reverse it. It is hoped that many will be helped by the information provided in this book. Personal Background: Dr. Leatherman has been balding for over 40 years and has tried nearly all of the various types of remedies suggested above, excluding systemic therapies and surgical solutions. It is not that he is opposed to surgery having owned the Desert Surgery Center in Palm Springs, California, and the 180 bed - Bay View Medical Center in San Diego, California, and the Nu-Image Institute (a licensed cosmetic surgery center also in San Diego) but because he was a Classification No. 7 on the Norwood scale and therefore not a candidate for any surgical options. He discloses to the readers that he is presently using, manufacturing and distributing ReGenrXx Hair Serum 90. He had previously used many of the various treatment options referenced above with no personal success. He is now growing hair on his Norwood category 7 scalp. Unlike many, he was cue ball bald nothing was noticeably growing on his scalp, not even hair fuzz (vellus hair). Because of his personal success and the success of others he has decided to co-author this eBook with the developer of AQ Advanced Hair Complex +, Dr. Ahmed Al-Qahtani, M.D., Ph.D. Both authors hope to benefit others seeking new advanced solutions of hair enhancement. The objective of this eBook is to provide a logical, rational, plausible and scientifically supported option in the management of hair loss. The renewing of the hair follicle to a state of health and the mechanisms available to accomplish this is the target focus of this undertaking.

INTRODUCTION

BreakingNews:BaldnessReport
ANewScientificReportfromUniversityofPennsylvaniaPointstoaSolutionfor HairLoss: WakeupthesleepingStemCells.

Today, many, if not all of the 80,000,000 Americans suffering from hair loss are seeking the information contained in this eBook. The University of Pennsylvania researchers just released new facts which disclose that the problem with hair loss is not that the scalp lacks stem cells but rather that they may simply be asleep and no longer conscious enough to be able to produce the progenitor cells (the work horses) involved in the regrowth of hair. Signaling molecules, sometimes referred to as growth factors, are natural and naturally occurring secretions from stem cells that are assigned this communication task to stimulate the development and function of these progenitor cells that grow hair. This book is designed to help you and others find out about the latest scientific advances and explanations in hair loss research. It is hoped that this knowledge might shed new light and understanding on why the techniques and products in todays market either work or do not work. This eBook is a bit technical but the authors have attempted to simplify the concepts without losing the valuable information obtained from the referenced research studies. The book offers the reader added understanding of his options in achieving hair follicle and hair growth enhancement. You may not need to WAIT FOR ANOTHER 10 YEARS to take advantage of effective therapies. The information in this book is straight forward and scientifically supported. Reading the book will provide you with better decision making about which products on the market to buy or not to buy, try or not to try. Many physicians and medical researchers agree that potent stem cells and their normal and normally secreted signaling molecules are the future of medicine. Many believe that this FUTURE is here TODAY. Many doctors and researchers also believe that stem cell derived growth factors and signaling molecules may hold the key to unlocking a permanent solution for hair growth and balding.

CHAPTER I HOW IT WORKS:


The Science behind Stopping Hair Loss And Re-growing Hair With Growth Factors One of the recent discoveries that evolved from stem cell research is the isolation of powerful molecules that work like light switches. As these signaling molecules that are natural and naturally secreted from the stem cells come into proximity with non or sub functioning tissues and organs of the human body they almost magically repair the cells and tissues that were malfunctioning and restore them to their intended function. To provide the reader with some knowledge of the power or potency of these growth factors, a study is cited: Please remember that these signaling molecules that are referenced herein are naturally secreted. Due to space limitations only one such example of potent signaling molecules that address ALZHEIMERS in mice from the University of California - Irvine is sited herein. There are thousands of similar examples found in validated stem cell scientific literature. The entire article was published in CIRM (California Institute for Regenerative Medicine Annual Report 2009.) CIRM was established by Proposition 71, the California Stem Cell Research and Cures Initiative, which provided $3 Billion in funding for stem cell research at California universities and research institutions. We quote their official publication annual report: ALZHEIHERS DISEASE RAVAGED THEIR BRAINS. Unsurprisingly, their memories were worthless. They could be shown the safe harbor in a water maze-a test of mouse memory-every day and never remember where it was. Frank LaFerta, Ph.D, director of the Institute for Brain Memory Impairments and Neurological Disorders at the University of California, Irvine, didnt believe that stem cells held promise for ALZHEIMERS patients. But he let experiment decide the question. LaFerta and his team injected neural stem cells into the hippocampus of the doddering mice. A month later, he put the mice into the water maze where they had failed so miserably before. This time, the animals learned. They remembered. They performed every bit as well as their ALZHEIMERS FREE peers. But it was puzzling. When LaFerta looked at the brains of the stem cell treated mice, the diagnostic markers for Alzheimers disease-amyloid plaques and neurofibrillary tangles-were still there.adding to the puzzle only a few of the new cells turned into neurons. But when LaFerta looked more closely, he found the brains learning center, the hippocampus, had new wiring-a dramatic increase in new connections between neurons, called synapses. The remaining neurons were branching and touching and talking to a greater number of other neurons than they had before the stem cells were injectedFurther studies revealed that the stem cells kicked off this communications revolution by secreting something called brain derived neurotrophic factor, or BDNF. The stem cells also induced all the surrounding brain cells to squirt more BDNF. In fact, the researchers were able to inject BDNFand induce synaptogenesis, but at half the level induced by stem cells. This suggests that secreting BDNF (growth factor) is only part of what stem cells do, LaFerta said. We got into this not expecting it to work. Now we know stem cells dont need to replace neurons. By implanting stem cellsthere is almost a doubling of synaptic density. This published review of LaFertas work addressed a new awarenessthat stem cells secrete a natural communicating or signaling molecule, BDNF that improves synaptic communication. Now we know even more: for example that there are more than 200 of these powerful molecules secreted by stem cells in the form of growth factors, cytokines and other communicating molecules, Wnt proteins, sonic hedgehogs, etc., that perform similar functions in cells throughout the body. These stem cell secretions

that are squirted onto mal-functioning cells do so to heal the unhealthy cells and restore normal function. It appears not to be necessary, in most instances, to actually replace the cell. Think for a moment about the complex organ of the hair follicle. It consists of many tissue types: muscles, glands, skin (ectoderm and mesoderm), nerves, the hair bulb with stem cells, etc. Each hair follicle is an organ and on the scalp there are hundreds of thousands of hair follicles. When hair loss or balding occurs it is because this hair organ has been compromised. There are many reasons for this compromise which the authors will not address in this writing other than to mention the diminishing of the number of progenitor cells and subsequent minimizing of the hair shaft. Suffice it to say that the cause does not matter as much as the solution. Explanation: a study of stem cells has revealed something unheard of prior to knowledge of this advanced science. The bodys components have seemingly infinite abilities to heal all specialized cells in the body. When a tissue malfunction occurs, the medical physician performs a diagnosis and then prescribes a drug to combat that diagnosis. Sometimes this exercise results in the prescription of multiple different medical prescriptions , some with contradicting objectives and effects. We can easily be found to chase symptoms. The body focuses on solving the underlying problem. Dr. LaFerta uncovered a small part of this big picture: that the natural secretions and naturally occurring secretions of stem cells can squirt the proper growth factor(s) in proper amounts to overcome and heal the tissue malfunction. If he waited to answer the question: what caused this malfunction, we would still be waiting for this valuable information. This does not mean to infer that the cause is not important. It is. However, it is not necessary to know the answer to that question in order to benefit from his discovery. The same is as true in hair loss as it is true in Alzheimers. Stem cells are primitive cells that work like natural little pharmacies within the body that are standing by to heal the bodys damaged cells and tissues. Also, as discovered by Dr. LaFerta, more than BDNF is needed to overcome the symptoms of Alzheimers and that is why the naturally secreted powerful molecules delivered by the stem cells outperformed the medically injected BDNF administered by the research team. Therefore, in seeking an answer to hair loss we must focus on natural and naturally occurring potent stem cell secretions. These secretions are collected from Human Fibroblast Conditioned Media (HFCM). These secretions are generally referred to as growth factors, but they are more. In reality they are signaling proteins that communicate to enhance or repair a damaged cell or combination of cells. NOTE: Human Fibroblast Conditioned Media (HFCM) is classified as a 0 risk as to safety in cosmeceuticals. This means that they are universally considered safe for human use. Hair growth is maintained through a process that includes stem cell regeneration of hair follicles. The hair cycle consists of three defined stages: growth (anagen), followed by regression (catagen) and rest (telogen). Growth of a new hair requires re-entry into the anagen phase, a process involving activation of multipotent stem cells in the hair bulge. Activating signals originate from the dermal papilla, directing stem cells to regenerate the hair bulb, the structure from which a new hair will emerge. Multiple signaling pathways, including Wnts, Sonic hedgehog (Shh), and TGF-beta family members have been shown to promote anagen initiation. Genes interfere with this process and can result in premature balding. The external application of these signaling molecules from Human Fibroblast Conditioned Media (HFCM) appear to reconnect the lost signaling capabilities restoring the health to the impotent hair follicle. Androgenetic alopecia (AGA) is characterized by the miniaturization of the hair follicles in susceptible individuals and occurs in a defined pattern on the scalp. Hair loss in aging men and women is characterized by these damaged hair follicles. Normal hair growth depends on the hair cycle where periodic regeneration of the hair follicle, occurs through a stem cell directed process. Within the follicle normal stem cell function is essential for hair follicle regeneration. In studies of wound healing in burn victims and other patients there were observed the formation of new hair follicles and associated new hair growth. The formation of new follicles and hair growth was shown to be associated with a cascade of cellular and biochemical events during the wound healing process. By studying wound healing at the cellular and molecular levels, the skin was observed to have the ability to revert to a more primitive or embryonic state as progenitor cells migrate to the wounded area, restoring the regenerative capacity of the skin not previously thought to occur in adults. The regenerative

response included new hair follicle formation, allowing new hair to grow at the restored site. A major part of the wound healing cascade is the release of growth factors and cytokines from stem cells into the layers of the scalp at the site of the wound. These growth factors and cytokines function like a light switch, turning on lost or decreased function of the hair follicle. Although dihydrotestosterone (DHT) is only one factor, and a minor factor, in causing the unhealthy minaturization of the follicle in male pattern baldness process, it has received much attention. Several products are now on the market that attempt to restore hair growth based on interacting with the DHT pathway. These DHT specific products (e.g. Finasteride) have demonstrated limited efficacy and debilitating side-effects, including sexual dysfunction. Based on the similar etiologies of male pattern baldness through DHT, it was thought that naturally occurring growth factors may also benefit the treatment of AGA through the DHT pathway, but without the side- effects seen with other products such as minoxidil, a potassium channel agonist that affects heart function. More importantly, the direct effects of topically applied cytokines and growth factors to the hair follicle restores the normal physiology and anatomy of the hair follicle and is the critical factor in restoring hair growth. Below we report the first example of a placebo-controlled, double-blind study undertaken to examine the benefit of these naturally occurring growth factors in the treatment of Androgenetic alopecia (AGA). Objectives: The goal of this study was to test naturally occurring growth factors in the treatment of AGA. Subjects: Included in this study were males between the ages of 25 and 65 years of age, in good health, with mild to moderate AGA. Results: The results of this study showed a highly positive response to treatment. The blinded investigative staff assessment report showed that over 90% of study subjects dosed with the active study formulation were rated as improved at the final visit. Patient self-assessment demonstrated that 94% of the patients saw significant improvement in hair growth and prevention of hair loss.

Conclusions: This study establishes the effectiveness of naturally occurring growth factors for the first time in the treatment of hair loss. Growth factor technology has been used to generate completely new hair follicles for the first time in normal adult males. The researchers were able to induce the regenerative response, including new hair follicle formation, by applying a combination of factors to the scalp. This work showed that the application of these growth factors resulted in skin triggered molecular pathways, allowing a new topical treatment option for re- growing hair.

CHAPTER II NEW HAIR SCIENCE DISCOVERIES RELATING TO HAIR GROWTH


Scientists have discovered powerful molecules that are used in the signaling communications needed to maintain hair follicle health and also repair damaged or sub-functioning hair follicles.

Note: some of these growth factors inhibit hair growth so a composite mixture of growth factors will not be as effective in stopping hair loss or in the enhancement of hair growth. A carefully selected array of the available growth factors, protein molecules and cytokines, Wnt proteins, sonic hedgehog, etc., with significant potency will likely be needed to optimally induce hair follicle repair and enhancement of the hair follicle. CyGenX AQ Advanced Hair Complex formulation offers a powerful proprietary blend of these natural growth factors using patented technology and patented potent stem cell lines for the benefit of hair follicle health. A partial list of these growth factors are listed in the following graph. Endogenous substances that affect hair growth SUBSTANCE Basic fibroblast growth factor (bFGF) Platelet-derived growth factor (PDGF) Transforming growth factor beta (TGF- ) Interleukin 1-alpha(IL-1- ) Fibroblast growth factor type 5 (FGF5) Epidermal growth factor (EGF) Keratinocyte growth factor (KGF) Insulin-like growth factor I (IGF-I) Substance P Parathyroid hormone (PTH) 1,25 - dihydroxyvitamin D3 (1,25/OH/D3) SITE OF ACTION Dermal papilla cells Dermal papilla cells rDermal papilla cells Hair matrix cells Hair matrix cells Hair matrix cells Hair matrix cells Hair matrix cells Unknown Unknown unknown increase (M) decrease (M) concentration low = increase (H) high = decrease (H) EFFECT ON HAIR GROWTH increase (H) increase (H) decrease (H) decrease (H) decrease (H) decrease (H) increase (R) increase (H)

Table 1. Endogenous substances which affect hair growth. The species studied is noted in parentheses adjacent to the effect: H = human, R = rat, and M = mouse. It should be noted that there are vast differences between animal models and human hair follicles.

CHAPTER III THE BASIS FOR DHT AND 5 ALPHA REDUCTASE INHIBITORS
Two of the most common DHT blockers are topically applied minoxidil (Rogaine is the most common) a DHT blocker and orally and systemically ingested Propecia (finasteride), a 5 Alpha Reductase inhibitor initially developed to treat BHP (Benign Prostatic Hypertrophy) for non-cancerous enlarged prostate glands by reducing the testosterone hormone level in the male.

MINOXIDIL
DHT (dihydrotestosterone): DHT has received a lot of attention even though it is only one factor and a minor factor in the causation of hair loss. Scientific studies today report that DHT blockage and regulation is not only a natural function of the hair follicle but that it appears that restoring this function may be possible through squirting signaling molecules, such as growth factors secreted from stem cells into the area of hair follicle malfunction. This may, in turn, provide better and more permanent outcomes for hair loss sufferers. Products that contain minoxidil, and they are numerous, are sold to only temporarily interrupt the production of DHT. Once the use of minoxidil is stopped, all benefits are lost. After the FDA approved the drug years ago, Rogaine was sold under prescription and then as an overthe counter medicine until the generics were lawful to compete in the market place. Billions of dollars were spent on this product and billions more on generic replicas containing minoxidil under the protective guise that the primary ingredient of these generic products is approved by the FDA for the treatment of hair loss. Most of these generic products are minoxidil derivatives. Check the ingredient list on the product you are considering to purchase. If the product contains minoxidil, be aware that any positive benefits that are achieved will be lost shortly after stopping its use. A permanent solution is needed to solve this DHT buildup problem. NOTE: Solving the DHT problem is not the complete answer to hair loss as evidenced by the fact that many who use or who have used these DHT blocking products remain dissatisfied with their outcomes and are discouraged and understandably suspicious of any hair enhancing product introduced into the market. It appears that DHT was designed to be kept in balance by the optimally functioning hair follicle. Emphasis, therefore, needs to be placed more on the focus of obtaining maximum hair follicle health rather than simply blocking DHT. Today, it is possible to enhance hair follicle health, which enhancement may prove to be a permanent fix for hormone caused and other etiologically caused hair loss.

PROPECIA
The following is taken from the official site for Propecia and is an advertisement from the manufacturer. The authors do not endorse nor take liability for any representations made herein. PROPECIA significantly reduces DHT, a key cause of hair loss, by inhibiting the formation of DHT in your scalp. Reducing DHT appears to inhibit the further shrinking of affected hair follicles. DHT is a substance in the body that can shrink the hair follicle until it no longer produces visible hair. Scientists believe DHT and family history are key factors in hair loss. Learn more about the causes of male pattern hair loss.

DHT=dihydrotesterone. PROPECIA blocks the formation of DHT and, in this way, appears to interrupt the development of male pattern hair loss. PROPECIA helps reduce further hair loss and regrow visible hair. PROPECIA is the first and only FDA-approved pill proven to treat male pattern hair loss on the vertex (top of head) and anterior mid-scalp area (middle front of head) in men. PROPECIA was developed to treat mild to moderate male pattern hair loss on the vertex (top of head) and anterior mid-scalp area (middle front of head) in MEN ONLY. There is not sufficient evidence that PROPECIA works for receding hairlines at the temples.

PROPECIA is for the treatment of male pattern hair loss in MEN ONLY and should NOT be used by women or children. In clinical studies for PROPECIA, a small number of men experienced certain sexual side effects, such as less desire for sex, difficulty in achieving an erection, or a decrease in the amount of semen. Each of these side effects occurred in less than 2% of men and went away in men who stopped taking PROPECIA because of them. You may need to take PROPECIA daily for 3 months or more before you see a benefit from taking PROPECIA. If PROPECIA has not worked for you within 12 months, further treatment is unlikely to be of benefit.

PROPECIA can only work over the long term if you continue taking it. If you stop taking PROPECIA, you will likely lose any hair you have gained within 12 months of stopping treatment. Although results will vary, generally you will not be able to grow back all the hair you have lost. End of Propecia Advertisement The authors note that some have reported side effects from the use of Propecia but do not take a position on this matter. However, we do include the following link for those who have asked about those side effects. This is only one link and there may be others that may be accessed through independent Internet searches. http://www.propeciasideeffects.com Note: Sometimes the cure is more dangerous than the original condition. Everyone should be aware that all medications have side effects. In determining whether a particular treatment is the right one for you, please study and weigh out the long term consequences of your decision and insure that you are ready to take the risk. We advise everyone to first consult your physician before commencing the use of any medicine.

CHAPTER IV
J Clin Invest. doi:10.1172/JCI44478. Copyright 2011, The American Society for Clinical Investigation.

Research Articles
Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells
Luis A. Garza1, Chao-Chun Yang2,3, Tailun Zhao1, Hanz B. Blatt1, Michelle Lee1, Helen He1, David C. Stanton4, Lee Carrasco4, Jeffrey H. Spiegel5, John W. Tobias6 and George Cotsarelis1 1 Department of Dermatology, Kligman Laboratories, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 2Department of Dermatology and 3Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 4 Department of Oral and Maxillofacial Surgery, University of Pennsylvania School of Dental Medicine and University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA. 5 Department of Plastic Surgery, Boston University, Boston, Massachusetts, USA. 6 Penn Bioinformatics Core, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. Address correspondence to: George Cotsarelis, Department of Dermatology, Kligman Laboratories, M8 StellarChance Bldg., 422 Curie Blvd., Philadelphia, Pennsylvania 19104, USA. Phone: 215.898.9967; Fax: 215.573.9102; Email: cotsarel@mail.med.upenn.edu. Published January 4, 2011 Received for publication July 22, 2010, and accepted in revised form November 8, 2010.

Androgenetic alopecia (AGA), also known as common baldness, is characterized by a marked decrease in hair follicle size, which could be related to the loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from AGA individuals for the presence of hair follicle stem and progenitor cells. Cells expressing cytokeratin15 (KRT15), CD200, CD34, and integrin, 6 (ITGA6) were quantitated via flow cytometry. High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. These KRT15hi stem cells were maintained in bald scalp samples. However, CD200hiITGA6hi and CD34hi cell populations which both possessed a progenitor phenotype, in that they localized closely to the stem cellrich bulge area but were larger and more proliferative than the KRT15hi stem cells were markedly diminished. In functional assays, analogous CD200hiItga6hi cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings support the notion that a defect in conversion of hair follicle stem cells to progenitor cells plays a role in the pathogenesis of AGA.

Introduction
Adult somatic stem cells act as the ultimate source of cells for self-renewing epithelia during homeostasis and wound healing. In the skin, a portion of the hair follicle known as the bulge contains a reservoir of small quiescent stem cells that divide during the onset of each new hair growth cycle or in response to wounding (14). Here, we address whether bald scalp in androgenetic alopecia (AGA; also referred to as male pattern baldness) lacks hair follicle stem or progenitor cells. In AGA, large terminal follicles diminish in size with time, and the resulting miniaturized follicle eventually produces a microscopic hair. Miniaturization of the follicle takes place as the hair follicle cycles. All follicles continuously cycle from a growing stage (anagen), to an involutional stage (catagen), and then to a resting stage (telogen), before again entering anagen (5). In AGA, the new lower hair follicle that forms

at anagen onset is smaller than its predecessor. Testosterone is necessary for miniaturization, and 5-reductase type II inhibitors, which block conversion of testosterone to its more active form, dihydrotestosterone, delay progression of AGA (6). Little else is understood about the cause of AGA. Stem cells responsible for hair follicle cycling reside in the hair follicle bulge of both mouse and human skin (7, 8). Bulge cells generate all the epithelial lineages within the follicle (9), and their selective destruction leads to loss of the follicle (2). Isolated murine bulge cells, when combined with neonatal dermal cells in a skin reconstitution assay, re-form the entire cutaneous epithelium, including hair follicle, epidermis, and sebaceous gland (9, 10). Bulge cells give rise to a progenitor population called the secondary germ cells, which reside adjacent to the bulge during telogen and produce the new hair shaft at anagen onset. A new secondary germ regenerates from the bulge with each new hair cycle (1, 11). Human hair follicle bulge cells possess stem cell characteristics similar to those of mouse bulge cells. Proliferation studies on mouse skin and on human scalp grafted to immunodeficient mice localize quiescent cells to the bulge (3, 12). Gene expression profiles from isolated mouse bulge cells and microdissected human bulge cells share similar patterns (4, 9, 13). However, to our knowledge no human hair follicle cells have been reported to form hair follicles in reconstitution assays, likely because of limitations of the xenograft system. In vitro proliferation assays indicate that basal bulge cells possess a high proliferative potential consistent with a stem cell phenotype (13, 14). Global gene expression studies of isolated bulge cells from both mice and humans indicate preferential expression of the intermediate filament protein KRT15 and the cell surface marker CD200 (9, 13). CD34 expression marks hair follicle bulge cells in mouse, but not human, epithelium (7, 15). In humans, CD34 expression is confined to cells immediately below the bulge in the outer root sheath of the anagen hair follicle (7, 14, 16). These cells undergo apoptosis at the end of anagen, but cells from here form high numbers of colonies in in vitro assays and are considered to be a progenitor population derived from the bulge (14, 17). Thus, the use of these markers allows for assessment of stem and progenitor cell populations in human scalp. Here we analyzed KRT15, CD200, and CD34 expression with flow cytometry to assess the stem and progenitor cell compartments in bald and haired (i.e., non-bald) scalp from individuals with AGA. Surprisingly, we found that the stem cell population was maintained in bald scalp. However, CD200hiITGA6hi and CD34hi cells were greatly diminished. These lost cells likely represent early progeny of stem cells, based on their position in the follicle, stem cell marker expression levels, cell size, and cell cycle state. Functionally, an analogous murine CD200hiItga6hi population was capable of regenerating an entire hair follicle, consistent with a progenitor cell phenotype. These results suggest that loss of progenitor cells, but not stem cells, contributes to human male pattern baldness.

Synoptic Conclusion
Bald scalp in men with androgenetic alopecia (AGA) retains hair follicle stem cellsbut lack hair follicle progenitor cells Adult stem cells are the ultimate source for self-renewing epithelia (skin and scalp). A portion of the hair follicle known as the bulge contains stem cells that are present in balding scalps as well as nonbalding scalps. The researchers concluded that there is no lack of stem cells in the balding individual. This supports the conclusion that stem cell injection therapy is most likely not a necessary procedure for hair follicle enhancement. However, bulge progenitor cells do diminish in balding conditions. These bulge cells are important because they generate all of the epithelial cells, including hair follicle, epidermis, and sebaceous gland. They also give rise to progenitor cells called the secondary germ cells and produce the new hair shaft in the healthy hair follicle. This cycle is repetitive with each new hair cycle. Since the number of progenitor cells was greatly diminished in bald people, it was concluded that the diminishing of progenitor cells, not any lack of stem cells, is more likely the cause of the balding process.

Cytokines and growth factors influence hair growth. Possible implications for the pathogenesis and treatment of alopecia areata.
Rolf Hoffmann, Wolfgang Eicheler, Andrea Huth, Elke Wenzel and Rudolf Happle.
Archives of Dermatological Research, Volume 288, Number 3, 153-156, DOI: 10.1007/BF02505825

Abstract: Factors that influence the growth of the anagen hair follicle or initiate the switch to a catagen growth pattern have so far not been definitely determined, but there is increasing evidence that cytokines and growth factors play an important role during these processes. Recently we detected an aberrant in situ expression pattern of cytokines of the Th1 type (IFN, IL-2) plus IL-1 expression in untreated alopecia areata (AA), and a switch to high levels of IL-10 TGF-1 expression after successful treatment with the contact allergen diphenylcyclopropenone (DCP). Hence the question arose as to whether cytokines are able to arrest hair growth and whether IL-10 or TGF1 have the capacity to antagonize this process. Using whole-organ cultures of microdissected human hair follicles we studied the effect of a panel of cytokines and growth factors on hair growth and on the gross morphology of the hair follicles in vitro. IL-2, IL-10 and IFN- had no effect in this regard, whereas TGF1 partially inhibited hair growth and EGF, TNF and IL-1 completely abrogated it. EGF and TNF induced the formation of a club-like hair follicle, similar to catagen morphology of the hair bulb, whereas hair follicles grown in the presence of IL1 or TGF1 showed no particular morphological changes. We conclude that cytokines and growth factors are pivotal regulators of hair growth at least in vitro. IL-1 is suggested as playing an important role during the pathogenesis of AA. Possible mediators of therapeutic contact dermatitis (IL-10, TGF1, TNF, PGE2) are, at least in vitro, not able to antagonize the IL-1-triggered hair growth inhibition. Therefore, we infer that these mediators rather modulate the immune response in AA.

CHAPTER V Stem Cell Injection vs. Growth Factors for hair loss.
In brevity, stem cell transfer is probably not a viable prospect to solve the hair loss dilemma. There are a number of videos of this therapy available on the Internet. There are several reasons why this therapy may not yield the anticipated results, they are: First, clinically, scalp stem cell transfer failed for one of the co-authors of this eBook. Second, it is extremely rare that the stem cells implant and convert to other cell types. The primary function of the stem cell is to "repair" damaged cells by secreting these growth factors (signaling molecules) for the repair of deficient organic tissues and cytokines to repair deficiencies in the cytoplasm of the cells. Third, the stem cell is going to assess the "primary" need of the body and make those repairs. The body will always target the most anatomically dysfunctional and most significant priority or life threatening need first. Chances are, this will not be hair growth. If there is no life priority need, stem cells will simply remain implanted and remain dormant until a need arises. And lastly, there is no diminishing of stem cells in the bulge of the hair follicle. With no deficiency there is no need for implanting more. Note: One year post-op, one of the co-authors saw no change in hair growth from stem cell transfer.

Question: What is the problem? Answer: The diminishing number of progenitor cells.
The diminishing of progenitor cells can be genetic, hormonal, perhaps even nutritional and may be modified by enhancing the number of signaling molecules to stimulate the optimum homeostasis in the tissue component. This is hard to fully communicate, so please allow the following analogy. Picture, in your mind, all of the baseball coaches on the ball field. The coaches select their team players. The players all know their positions and each has a different function to perform on the team and on the field. Now, The catcher signals the pitcher what ball to throw. The pitcher signals back his response. The ball is pitched and the batter hits the ball. The first base coach signals to the runner to stop at first base or keep going to second base. Meanwhile, the runner at second base rounds third base and the third base coach signals the runner to stop at third base or to go to the home plate to score a run for the team. The coaches are not on the field and do not perform the function of the players, but are instead off the field and give signals to provide order and organization to the players. The coaches are the equivalent of signaling molecules. Everything that is needed to maintain hair follicle health is physically available, even adequate stem cells are found in reserve supply. What is missing is the coaching, or direction provided by the signaling molecules, to plan and execute the movement required so as to avoid minimization of performance, but rather to maximize performance. This is the job of signaling molecules in the body. This optimum signaling allows proper function of the hair follicle, the hair shaft, the sebaceous gland, waste elimination as well as the subsequent hormone regulation of DHT. In a state of homeostasis the cells achieve efficient performance rendering the hair follicle healthy and able to sustain a terminal hair shaft. This produces the desired result in the previously minimized hair follicle: homeostasis. The hair bulge is where scientists have found the presence of stem cells that grow hair. Stem cells are so hearty that they rarely die. They are considered immortal by classification. So it is doubtful that the need for new stem cells is the solution in re-growing hair. The "enhanced and directed stimulation" of the progenitor cells by the use of natural and naturally occurring signaling molecules that are designed to direct all of the classes of cells to a state of health and thereby perform their assigned functions is

gaining momentum in the battle against hair loss. The growth factors and other ingredients need to be blended to promote this signaling capability and overcome cell deficiencies and restore the natural health of the hair follicle. NOTE: Depending upon the length of time the cells have been dormant suggests that this renewal process is not fast. It does require time for biological processes to repair damaged cells. If the hair follicle is dead (probably a very rare condition) then there is nothing that the dead tissue can do to react to the signaling molecules stimulus. A proprietary blend of hair stimulating growth factors and signaling molecules is essential to enable the enhancement of the hair follicle. Ample time for healing of the hair follicle is also required to permit the follicle to again grow vellus hair and finally to convert the vellus hair to terminal hair and sustain its growth. Because this hair-growth process requires a healthy hair follicle, the focus for hair follicle health must be the central objective of any effective hair growth product. Hair loss sufferers cannot afford to be impatient. Biology is biology and healing takes time. Those seeking a real fast (immediate) solution may need to seek out a hair replacement company to fit a hair piece, because nothing that we know can speed up this biological process. Note: One of the coauthors has worn a hair replacement for over 27 years and continues to do so while he applies the Hair Serum simultaneously with the use of his hair system and plans to continue to do so until he achieves his optimum hair expectations. Both uses are compatible. Note: Remedies in the form of medications approved by the FDA that focus solely upon DHT influences ignore by their very focus, the repair of the hair follicle. They are at best, band aides with associated side effects that may be harmful to the individuals overall health. Here, then, is a good standard by which anyone can measure the potential efficacy of any and all seriously considered products: what is the products realistic capability to positively affect the health of the hair follicle? And, does it have the potency to do so? And lastly, and most importantly, is it or are they harmful to the individuals health? Ultimately, in light of these new research findings, one must conclude that the primary cause for hair loss is the existence of unhealthy, non-functioning or sub-functioning hair follicles. To reverse that condition, it appears that signaling must be re-established to coax the stem cells that are in abundant reserves (even in the balding scalp) to develop the progenitor cells (the work horse) that regrows hair.

CHAPTER VI MECHANICAL DEVICES AND HAIR FOLLICLE HEALTH


There may be some mechanical advantage gained by the use of the derma roller and also Low-level Light Laser Therapy (LLLT) in hair stimulation. The AQ Advanced Hair Complex manufacturer instructs the massaging of the scalp for five minutes with each application. There are mechanical advantages offered by this massage recommendation. One of these benefits is increased circulation of blood flow into the area of the scalp as well as deeper penetration of the signaling molecules into the epidermis. Theoretically, this may promote the healing process, however, probably not optimally, without the application of the signaling molecules. Certainly, if one is going to take the time to massage the scalp for five minutes, it only makes sense to first apply the needed molecular direction to the hair follicles. Balding and hair loss suggests malfunction and deficiencies within the hair follicle largely because the stimulating signaling molecules are absent or in short supply. They MUST be supplemented. The aging process is a normal causative factor in the mal-functioning process of hair loss. However, with external application of certain potent signaling molecules hair follicle health has been observed. The key to avoiding Hair Loss is not to ignore it. There is much that can be done if hair follicles are still alive. Once follicles are dead there is nothing that is known that you can be done to bring them back to life, so if you notice changes in hair growth, thinning or fall-out, see a doctor and a hair loss specialist! Using low-level Laser Hair Therapy may give sleeping hair follicles a boost and it can work in conjunction with other treatments for perhaps even more positive results. Typically youll want to check with your primary care physician and a dermatologist to determine why youre losing your hair first, because this LLLT works only for certain hair loss conditions. Low-level Laser Hair Therapy is an adjunctive therapy that may have some value for male baldness that is caught early (within the first five years of hair loss). It can be administered through a hand- held unit or a whole head unit you might find at a hair loss clinic or studio. This hair loss treatment has been approved by the FDA to promote hair growth in males with Male Pattern Baldness who have Norwood Hamilton Classifications of I to V. The unit looks like a hair brush or comb with diodes and LED lights that distribute low- level laser light to the scalp while the comb teeth simultaneously part your hair so it reaches the scalp. Because hair is meant to fall out and re-grow from the roots, when follicles begin to shrink and degenerate, the hair does not grow back and hair loss occurs. Studies showed that the laser light therapy, when used on a regular basis can strengthen and regenerate shrinking follicles to grow again. The laser light, especially if used in conjunction with other hair growth stimulants may increase blood flow to the scalp and jump-start hair follicles to do what they are intended to do. This slows down hair loss and in many cases reverses the degenerative cycle and stimulates a live follicle to produce more, thicker, stronger, healthier hair. However, like MInoxidil and Propecia, LLLT is only good while receiving the administered therapy. Any benefits that are achieved will be lost with cessation of treatments.

CHAPTER VII VITAMINS, MINERALS, HERBS and ORGANIC INGREDIENTS IN HAIR FOLLICLE HEALTH
The authors do not intend to examine ingredient by ingredient all of the numerous natural compositions that are recommended for hair health. This would be an exhausting and extensive undertaking that exceeds the scope of this book. There are, however, some directions that can be offered to help the reader to evaluate each one of these products globally. Remember, that one of the co-authors has extensively studied and recommended certain natural supplementation in clinical practice. The authors are supportive of organic substances, nevertheless, there are global limitations which are explained below. (When the word vitamin is used hereafter it is meant to refer to all of the organic compounds that are listed as ingredients in hair promoting products.) If ingredients do not convert into needed nutrients and oxygen in the cellular mitochondria or are not readily convertible into ATP, they are useless. The argument may appear to be scientifically validated in a products marketing materials concerning the need for nutrients, but only that which is available for ATP conversion within the mitochondria of the cell has the ability to nourish the cell. In most cases there is not a nutritional uptake problem in balding individuals so supplementation of these nutrients may very well prove as unsuccessful efforts to regain hair that has been lost. That is why vitamins, herbs, minerals, etc., have never been hugely effective in hair growth. Also, it is physiologically impossible to guide them into the tissues because they are ingested systemically. Vitamin intake is never the issue, but rather absorption and conversion. Absorption of the nutrients taken orally into the gut is only about 5 to 8%. Of that percentage it is unknown how much actually enters the blood stream and subsequently enters into the cellular membranes. Any molecule larger than 500,000 daltons will not pass through the cell membrane and is noted as worthless as a nutritional beneficiary for follicle repair. Vitamins encapsulated into liposome-type transport mechanisms may allow much higher concentrations of nutrients to pass from the intestine into the blood stream and thereafter into the cell membrane (perhaps as much as 80%). This technology is available today, but perhaps due to the higher cost of manufacturing these products, very few vitamins are available in this form. Nevertheless, this nutritional boost might be helpful for many conditions affecting poor health that are validly associated with nutritional deficiencies. It is unknown, if or how long it might take for nutrients to heal a hair follicle sufficient enough to overcome the minimization of the hair follicle process, if that is even possible. The challenge is to direct this supplementation to the follicles to repair it and hence the hair shaft. You can visualize in your mind this to be nearly an impossible task. However, supplementation of the needed growth factors locally, at the site of hair loss, is easily achievable. With the addition of Penetration Plus Nano-Encapsulation Technology, the efficient passage of these growth factors through the stratum corneum or epidermis is greatly enhanced. This would suggest better and faster hair growth results. One thing is for sure to this author, natural vitamins will do no harm, which ought to be the first concerns of all health practitioners along with efficacy of the product (does it work?). The Startum Corneum There are two primary ways to ingest products. The first is through absorption from the intestine and the second is through the skin via topical applications. Briefly we address the topical solution passage through the stratum corneum. There are many ingredients that are complex proteins or other molecular forms found in many hair growth formulations that exceed the absorption limitations (500,000 daltons) of the cells of the body.

Translation: they are too large to pass through the epidermis of the scalp (stratum corneum). It is easy to see that the products containing these large molecular forms cannot obtain efficacy because they cannot pass through the outer skin. These formulations, excluding those containing natural and naturally occurring signaling molecules because of their smaller sizes, simply cannot and do not work due to the bodys own physiological and anatomical defensive mechanisms. The bodys own skin is a protective barrier wall of dense dead epithelial cells designed to not permit passage of foreign substances including viruses and bacteria to prevent infections and other harmful reactions. Only those ingredients that are anatomically small enough and safe enough (nave) are allowed to cross this barrier. That being said, with new technological breakthroughs in molecular transport, the smaller proteins could be made to ingest into the circulatory system and subsequently into the cell membrane. However, large molecular structures over 500,000 daltons probably cannot penetrate the stratum. Compounds of less than 50 amino acids appear to pass through the cell wall into the nucleus while those larger than 500,000 daltons or 50 amino acids do not. This means that non-absorbed ingredients, no matter how valuable or how badly needed by the body, sit on top of the epidermis, doing nothing but perhaps clogging the pores and await the next shampooing to be removed.

Conclusion
Growth Factors or signaling molecules are required to maintain homeostasis throughout the body. Although this book references specifically the hair follicle, it is accurate to represent that the principles affecting the hair follicle are just as applicable to all other tissues and organs of the body. This small focused science is potentially the most massive and powerful discovery of our time to date. The implications are equally massive for the restoration of non-functioning and sub functioning tissues in every organ of the body. The prospect of being able to reverse Alzheimers, diabetes, neuromuscular disorders of all types, and other conditions too numerous to mention is mind staggering. Although hair loss is not life threatening, it is a huge challenge that affects millions, even hundreds of millions throughout the world. The implication we make is that restoring function to the hair follicle is one step, perhaps the first step in a long array of functional restorations in the future. The power to restore function is held within the miraculous human body and the release of its amazing power over the upcoming years will be an exciting journey to behold. Putting an end to the suffering from chronic and debilitating diseases and conditions is an undertaking worth our greatest efforts. We are on the brink of great therapeutic activities, globally. Today, the uncovering of small signaling molecules lays a foundation for better and more accurate delivery of potent growth factors to restore the hair follicle to health, naturally. The passage of these small molecules permits their transport into the dermis through the openings of the hair follicles, even one that is minimized in size. Furthermore, the signaling molecules do not need to enter into the cell membrane to assist the repair process, but direct it from a distance because, remember, they are signaling molecules and function quite well from a distance from the cell activity. The ability to stimulate the stem cells housed in the human scalp to activate the production of progenitor cells and restore health to a dormant hair follicle and hair shaft is only the beginning. Tomorrow is an exciting day to contemplate.
Thank you for Reading this eBook. We hope that it has been helpful. CyGenX
ThestatementsinthisbookhavenotbeenevaluatedbytheFoodandDrugAdministration.Theproduct:CyGenXAQAdvancedHairComplex+isnot intendedtodiagnose,treat,cureorpreventanydisease.Individualresultsmayvary.CyGenX,Inc.,2011.