Global DHI RESEARCH

AND DEVELOPMENT

update By Cali Giannatou- Marketing Dept.

December 2011

1- DHI study of the use of ACell

Extracellular Matrix in Direct

Hair Implantation

• ACell’s Extracellular Matrix (ECM) is a natural biological material that can be implanted

at the site of an injury or damaged tissue in order to stimulate healing.

• The graft stimulates the body’s own cells to form new tissue specific to that site

(a process referred to as “Auto-cloning”).

• Therefore, instead of the body producing scar tissue, the body heals by remodeling with new tissue, almost as if the injury had never occurred.

• DHI’s research on ECM has shown rapid tissue remodeling

by promoting neovascularization (growth of new blood vessels)

and recruiting host-derived mesenchymal cells (cells that lay down

collagen and potentially can promote the formation of hair).

These effects result in quicker healing of wounds and less scarring.

• The possibility of using a biologically-derived matrix to enable hair

multiplication is real, but significant work remains in order for hair

multiplication to become a practical treatment for hair loss in men

and women.

• DHI is currently studying the use of ECM for scalp hair multiplication,

as well as the facilitation of wound healing in follicular unit

transplantation procedures.

2-DHI STUDY ON PRP Platelet

rich plasma DHI has implemented PRP (Platelet Rich Plasma) in several cases, testing the hair loss treatment

with addition of DNA Activator, which is an innovative method for the treatment of male & female hair loss.

PRP is based on the enrichment of blood plasma with platelets through specialized process and its direct injection to the area affected by hair loss. PRP appears to be a highly effective hair loss treatment & hair transplant reinforcing treatment.

PRP protocol PRP injection is implemented under strict specifications of hygiene & safety by the specialized physicians and biologists-biochemists through the following protocol:

1. Blood taking (as when in general blood testing) up to 50cc 2. Blood centrifugation in order to isolate the plasma 3. Enrichment of the plasma & the white phase with

DNA Activator 4. Infusion of the multi-potent enriched plasma to the area affected

by hair loss (topical anesthetics have been previously administered)

2-DHI STUDY ON PRP Platelet rich

plasma

• In which cases do we implement PRP? PRP treatment is implemented to men & women who suffer from hair loss at early or advanced stages:

For the treatment of Androgenetic Alopecia -as a supportive treatment to Hair Transplants -for the prevention of hair loss

• PRP results Significant results have been observed in hair loss treatment, mainly due to the fact that hair loss can be reversed and the result can be preserved.

• DHI is currently evaluating the results of patients with PRP implementation

3- Approaches to identifying

disease genes

HAROKOPIO UNIVERSITY

Department of Dietetics & Nutritional Science

Familial linkage analysis

An established approach utilizes multigenerational families with affected and unaffected members.

Diseases in which the phenotype is expressed at a relatively young age and in a consistent manner

allow confident phenotyping.

Therefore, the familial linkage approach is best suited to diseases with robust phenotypes that are

caused by single genes.

Given the sexual dimorphism of androgenetic alopecia, it is not possible to confidently characterize

phenotypes in women. Furthermore, the age-dependence of phenotype expression in men

reduces certainty of the unaffected phenotype in younger individuals.

As such, the pedigree linkage approach is not suited to a study of

androgenetic alopecia

3-Affected sibling-pair linkage

analysis Affected siblings presumably have a 50% probability of sharing any genetic marker by chance; however,

bald sibling pairs will share a causative genetic mutation more often than 50%. If such a deviation from

chance sharing is detected for a chromosome region or specific gene, that gene or region may linked to

baldness.

Candidate genes can be assessed individually.

In addition, it is now possible to examine the entire genome, chromosome by chromosome (termed a

genome-wide scan), relatively quickly and inexpensively for linkage.

Current estimations of the number of pairs required for sufficient statistical power range from 300 to 400

pairs

HAROKOPIO UNIVERSITY

Department of Dietetics & Nutritional Science

Prevelance of Alopecia in 1000 men

62%

38%

Yes No

3-case control association studies

This form of analysis involves selecting affected individuals (cases) and unaffected individuals

(controls) from the population, and comparing the frequencies of alleles of candidate gene variants.

The definition of cases is important. In progressive conditions with variable ages of onset such as

androgenetic alopecia, it is often difficult to accurately phenotype individuals as “unaffected,”

particularly in younger individuals.

Factors such as population stratification (eg.case group are racially different to the control group) can

affect the allele frequencies of common polymorphisms and lead to false positive results.

HAROKOPIO UNIVERSITY

Department of Dietetics & Nutritional Science

3-Insidence

11% of the men aged 18–30 years, have been identified as having cosmetically significant

baldness (type III or greater on the Hamilton baldness scale) and selected as the most

genetically predisposed case group. In addition, 21% of the men aged 50 years or greater,

were identified as having no indication of baldness (type I on the Hamilton baldness scale)

and were selected as the least genetically predisposed control group

HAROKOPIO UNIVERSITY

Department of Dietetics & Nutritional Science

Prevelance of Common Alopecia Classifications

frontal &

vertex

36%

frontal

40%

vertex

24%

frontal vertex frontal & vertex

3- what genes are related to

androgenetic alopecia?

A variety of genetic and environmental factors play a role in causing androgenetic alopecia.

It has been determined that this form of hair loss is related to hormones called androgens,

particularly an androgen called dihydrotestosterone.

Androgens are important for normal male sexual development before birth and during puberty.

Androgens also have other important functions in both males and females, such as regulating hair

growth and sex drive.

HAROKOPIO UNIVERSITY

Department of Dietetics & Nutritional Science

Age of Hair Loss (years)

Mean 39

Minimum 15

Maximum 75

3-The AR Gene

The AR gene provides instructions for making a protein called an androgen

receptor. Androgen receptors allow the body to respond appropriately to

dihydrotestosterone and other androgens. Studies suggest that variations

in the AR gene lead to increased activity of androgen receptors in hair

follicles. It remains unclear, however, how these genetic changes increase

the risk of patterned hair loss in men and women with androgenetic

alopecia.

HAROKOPIO UNIVERSITY

Department of Dietetics & Nutritional Science

3-Other candidate genes

5α-reductase. It is responsible for the reduction of testosterone to the more potent DHT. Type I 5α-

reductase is encoded by the SRD5A1 gene on chromosome 5, and type II 5α-reductase is encoded by the SRD5A2

gene on chromosome 2. Both forms of this enzyme are expressed in hair follicles. In a case control study, lack of

association

Insulin. There appears to be a strong association between levels of insulin and levels of sex hormone binding

globulin and of testosterone. Also, insulin has been shown to be important in the regulation of the timing of the

growth (anagen) and rest (telogen) cycles of the hair follicle. Again negative results

HAROKOPIO UNIVERSITY

Department of Dietetics & Nutritional Science

Hair follicle

Aromatase. It is responsible for the conversion of C19 androgens such as testosterone to estrogens. It is decreased

in balding scalp. Again negative results

Estrogen receptors. It may be involved in the regulation of the hair follicle cycle in mice. Treatment with

estrogen receptor antagonists caused telogen hair follicles to move into anagen phase, initiating hair growth. Again negative

results

Growth factors. The insulin-like growth factors (IGF) and vascular endothelial growth factor (VEGF). The IGFs

have been shown to play a regulatory role in hair follicle cycling. IGF2 negative results. IGF1 and VEGF unknown

HAROKOPIO UNIVERSITY

Department of Dietetics & Nutritional Science

3-Other candidate genes

3-Ectodysplasin A2

receptor: EDA2R gene

Mutations in EDA give rise to a clinical syndrome

characterized by loss of hair, sweat glands, and teeth. The

protein encoded by this gene specifically binds to EDA-A2

isoform. This protein is a type III transmembrane protein of

the TNFR (tumor necrosis factor receptor) superfamily, and

contains 3 cysteine-rich repeats and a single

transmembrane domain but lacks an N-terminal signal

peptide.

HAROKOPIO UNIVERSITY

Department of Dietetics & Nutritional Science

3-Our aim

To recruit 1000 individuals and estimate the incidence and the grade of male

pattern baldness (by the Hamilton and Norwood grades)

To genotype for the rs2180439 variant in our population

To assess the dietary intake. Hair loss has been correlated with Iron and/or

Zinc intake

To analyze for gene-diet interactions and the male pattern baldness

HAROKOPIO UNIVERSITY

Department of Dietetics & Nutritional Science

0

10

20

30

40

50

60

70

Yes (38,9%) No (61,1%)

Positive history of alopecia

Negative history of alopecia

4-HAIR MULTIPLICATION

• It is a process similar to hair cloning; • Cells are extracted from hair follicles, they are multiplied in vitro and then re implanted to the thinning

area, in order to produce new hair follicles • Researchers have observed that connective tissue cells (Fibroblasts), which lie in the rear most part of

hair follicles, can be more easily reproduced in vitro than other cells of the hair follicles. After the extraction of hair follicles from the donor area, researchers can separate connective tissue cells from hair follicles and cultivate them in vitro in order to create new hair follicles. Fibroblasts are multiplied under laboratory conditions and then they are placed on the thinning area of the scalp in order to start growing.

• Hair cloning can produce new hair. Hair cloning could allow patients with insufficient donor area supply to become suitable candidates for hair transplantation. Hair cloning research focuses on the following issues:

• The form of cells that will be selected for reproduction (as there are many other forms of cells apart from fibroblasts)

• Effective cell cultivation and reproduction in vitro

• Proper placement of new cells in the thinning area in order to attain the desirable pattern of growth • There is much dispute as to when hair cloning will be a widespread technique with proven effective results

in hair loss treatment. This cannot possibly happen in the near future, as many years of research are sure to follow.

5-IMPROVED DIRECT HAIR

IMPLANTATION TECHNIQUE

6. Direct hair

implantation in burns,

traumas & scars

DHI was implemented to scars as well as to burns and traumas. DHI is currently under evaluation of the after session growth of hair in traumas, burns and scars and is evaluating the results and the percentage of growth

7. Direct hair

implantation stencil

DHI is currently evaluating the use of stencils and transparencies to mark the recipient areas, for even distribution of the extracted hair follicles

8-NEW CHAIR FOR DIRECT

HAIR IMPLANTATIONS

DHI is under the process of designing a new chair for Direct Hair Implantation

9-New surgical table

DHI is currently studying the offers and the specifications of the new surgical tables to be ordered

10-New pillow for

direct

11-New needles and

punches

DHI is currently under negotiation for the

exclusive design of needles as well as 08 and 07 mm punches exclusively designed for DHI

12-Hair implantation

powered tool

DHI is experimenting in ultra modern powered extractors with high extraction speed and electric extraction machines for quicker scalp and body hair extraction .

13-Hair extraction unit

DHI is investing in an ultra modern robotic extraction system, with high extraction speed, for scalp and body hair extraction . A special software and a pc operator, define the given angles, the spaces, the desired density and other parameters, for successful extraction results

14- Presence at global

Congresses and Events

• IMCAS India 2011 Nov 13, 2011 New Delhi India • EMAA, 7th European Congress of Aesthetic Dermatology, Aesthetic Surgery

and Anti Aging Medicine, in Paris France on Sept 30th-Oct1st 2011 • Poster Presentation at ISHRS 19th Annual Scientific Meeting in Anchorage

Alaska, 14th - 28th September 2011 • Annual Dermatological Meeting at Zappeion Congress Center, Athens, Greece,

on the 12-14 of May 2011 • Cosmetic News, London - UK, May 6th and 7th, 2011 • ISHRS FUE Conference - Istanbul Turkey, 12th May 2011 • 11th Annual Dermatological Meeting - Athens, Greece, 13-14th May 2011 • Aegean Masters Meeting - Athens, Greece, 28 & 29 May 2011 • IMCAS Singapore Asia July 17, 18, 19, 2011 • DHI Founder, Mr. Konstantinos Giotis will be present at the annual meeting

"Chirurgie Restauratrice du cuir cheveaux : D.I.U" which will be held at the Eduard Herriot Hospital place d‘ Arsonval on May 12th, 2012

14- Presence at global Congresses

and Events

15-Psychological aspects of hair loss

Ethnic Differences - global study

50%

36,48%

29,72%

12,16%

12,16%

8,10%

Greatest Achievement

Θ Τεχνική DHI DIRECT

DHI Total Care System

40 Χρόνια Εμπειρίασ

Πρώτη Κλινική Με ISO και CQC

Πάνω Από 100.000 Ευχαριςτημένοι

Παγκόςμια Παρουςία

36,48%

32,43%

25,67%

18,91%

9,45%

2,70%

Effect of hairloss in the Daily Life

Ψυχολογικό Στρεσ

Προςωπική Ηωή

Χαμηλή Αυτοεκτίμηςη

Κοινωνική Ηωή

Επαγγελματική Εξέλιξη

Κοινωνικέσ Διαταραχέσ

29,72%

25,67% 18,91%

16,21%

14,86%

2,70%

How did you get to know about DHI

Ζρευνα-Internet

Άλλη Πηγή

Φίλοσ-η

Διαφήμιςη-Τηλεόραςη

16-DHI PHOTO STUDIO

17-ALOPECIA TEST PORTABLE

WORKSTATION

18-www.dhiwebinars.com

This site is a useful tool and a valuable source of information and knowledge on: • Medical Options available worldwide • Pharmaceutical options • Non-medical Options • Natural Products • Research Projects • All Options on hair loss available today

19-Dhi on line training

academy programs

http://www.dhi.skillgate.com/dhi/index.cfm

On the DHI skillgate you will find over 40 first class on-line training programmes. (New programmes are added through the year.) These programmes form part of Academy10, a learning management system designed to offer full service learning support at an enterprise level. In addition to the programmes on offer, DHI can design and deliver training for DHI staff, manage performance, monitor their progress and keep records for regulatory purposes.

20-University Associations

for certifications

20-University Associations

for certifications

dhi will continue to tackle the global

challenges with constant RESEARCH AND

development

Welcome aboard