- Claims surrounding stem cell treatments are starting to get downright ridiculous - Various cosmetics lines have begun to market their goods as containing the benefit from plant stem cells - Many claims that these plant based stem cells will stimulate human stem cell growth and promote healthier younger looking skin- Plant stem cells as age-defying makeup creams? Seriously? Have we reached the point where we’re so enraptured with the possibility of human stem cell technologies that we’ll buy anything with ’stem cells’ in the product name?

I Can’t Believe The Hype – Beauty Products With Plant Stem Cells by Aaron Saenz on June 30th, 2010

- Are indispensable for growth and development in both animals and plants - Have two properties - Self-renewal : the ability to go through numerous cycles of cell division in an undifferentiated state - Differentiation : the capacity to differentiate into other cell types - May be able to repair or replace damaged tissue

♦ Have two basic types ♦ Embryonic stem cells (pluripotent) - are derived from the inner cell mass of an early stage embryo - are abundant in embryo and will give rise to numerous organs, tissues and cells in the body ♦ Adult or somatic stem cells (multipotent) - are undifferentiated among differentiated cells in a tissue or organ - generate all the cell types of the organ from which they originate – potentially regenerating the entire organ from a few cells

♦ Are responsible for refreshing tissues and compensating for cellular losses and are susceptible to degradation that comes with age ♦ Are rare and constantly lost in the tissues to make the tissues be less able to grow, maintain and repair♦ Growth may be uncontrollable and cancerous cells may reproduce causing tumors

Normal

Stem cells

Stem cells

Differntiated cells

Without C/EBP-beta

Epithelial skin stem cells in basal layer of epidermis and hair bulge stem cells in hair folloicle are basically found Epithelial skin cells are only capable of a certain number of cell divisions and then die off – they are shed constantly and require continuous duplication of new cells Partly become fibroblasts responsible for collagen, elastin and hyaluronic acid productionA loss is detrimental to the skin (one ages skin stem cell division diminishes dramatically causing in wrinkles and thinned skin)

● Have the ability to regenerate the whole plant(any kind of cell or tissue) ● Have a much longer life● Have a built-in mechanism that, which causes the cell to ‘self destruct’  if damage to the DNA is detected and defective DNA will not be passed on ● Cannot make damaged or cancerous cells reproduce themselves

● A callus tissue is formed when a plant is wounded ● The normal differentiated cells in the callus tissue go back into a dedifferentiated form and become stem cells● Mechanism is controlled by different plant hormones (auxins)

Stem cells

Reprogramming of P. patens leaflet cells into stem cells and subsequent protonemata development

Day 2 Day 3 Day 6

Dead cells

Stem cells grown into filamants

Development into protonemal colony

Stem cells

Stem cells can make identical copies of themselves as well as generate specialized cells

Progenitor cell (stem cell)

Transient amplifying cell

Differentiated cell

- H ave an essential role in coordination of many growth and behavioral processes in the plant life cycle

- The important ones include 4-chloro-indoleacetic acid, phenylacetic acid and indole-3-butyric acid- May induce the cell differentiation and regeneration of the vascular tissues when plant is wounded- Provide the ability to regulate protein synthesis (evidences showed the potential to promote collagen and elastin) - Only found in plant stem cells- Are not present in the adult plants

□ Contain compounds that are beneficial for human health and beauty. They are vitamins, minerals, oligoelements, growth enhancing hormones (e.g., auxins, gibberellins), cytokinins, nucleic acid and enzymes essential for plant growth many interesting plant substances (e.g., flavonoids) with new, powerful multi-functional and special properties e.g., detoxifying, UV stress protection □ Potentially cope with environmental stress

GMO-free Sustainable eco-friendly Allows utilization of even the most rare plant species without harm Free of heavy metals, pesticides, and other environmental contaminants  No limitation of plant sources due to any restrictions Rare active molecules of interest can be concentrated up Can be developed exclusively to meet one’s needs Safe for both cosmetic and nutritional applications

Plant Stem Cell Technological Process (Example)

Taking away a small piece of the plan

Wounding of plant material to induce callus formation

Incubation on agar plates

Harvesting of developed callus

Cultivation until complete dedifferentiation to obtain stem cells

Transfer of the stem cells into a suspension and grow

Growing into plants

Are compatible with human skin Protect human skin stem cells Maintains the self renewal capacity of human skin stem cells Increase longevity of human skin stem cells Replenish, regenerate and repair damaged DNA Delay aging of essential cells Stimulate duplication of human skin stem cells Protect the skin from ozone/pollution damage and UV damage

Origin Trade name Source- Panax ginseng (Wild Korean ginseng)

- ActostemR WKGBASE- ActosomeR GINLIFT

ACT, Korea

- Cyperus papyrus (Papyrus)

- Crodarom Papyrus Crodarom,France

- Buddleja davidii (Summer lilac)- Centella asiatica (Asiatic pennywort)- Echinacea angustifolia (Echinacea)- Leontopodium alpinum (Edelweiss)

- Buddleja davidii Stems GTM

- Centella asiatica Stems GTM

- Echinacea Angustifolia Stems GTM

- Leontopodium Alpinum Stems GTM

IRB, Italy

-Rhododendronferrugiineum (Swiss Alp rose)- Malus Domestica (Apple)- Vitis Vinifera (Grape)

-PhytoCellTectTM Alp Rose

- PhytoCellTecTM Malus Domestica

- PhytoCellTecTM Solar Vitis

Mibelle Biochemistry, Switzerland

Rhododendronferrugiineum

Increase skin cell vitality; boost epithelial regeneration; help skin to cope with climate changes

Buddleja davidii

Protect photodamage and oxidative stress; offer complete treatment for acne disorders

Leontopodium alpinum

Reduce eye contour and collagen loss; prevent photoaging

Echinacea angustifolia

Promote collagen; revitalize dull, tired skin

Malus Domestica

Preserve the youthful look a nd the vitality of skin

Vitis Vinifera Protect skin stem cells against UV stress, fight photoaging

Centella Asiatica

Firm skin; improve skin tone and elasticity

Cyperus papyrus

Moisturize, soothe and energize the skin

Pinax ginseng

Reduce wrinkles; inhibit adipo-cyte differentiation

Edelweiss

Grows spontaneously on mountains range from Pyrenees and Alps to Himalaya

Develop many defensive mechanisms in order to survive the extreme heights and protect from high level exposure to solar radiations

From Edelweiss, the symbol of “Alpine flora” with the aid of High Tech Nature (HTN) biotechnologoy

Callus

HTN biotechnology is the unique process that allows the in vitro culture of plant stem cells in highly controlled conditions and enables to produce the active substances with several innate advantages : - be able to produce substances that are rare and difficult to obtain from nature or synthesis - secure the growing stem cells from pesticides, heavy metals and aflatoxins - possibly obtain stems cells from endangered or protected plants without altering the ecological balance and biodiversity - supply plant products independent of climatic and geographical variability

> Reduction of eye contour wrinkle > Prevention of collagen loss> Firming and restructuring treatments > Prevention of aging and photo-aging

Cosmetic Use

contains specific substances with high biological activities - Leontopodic acids A

and B, chlorogenic acid, 3,5-dicaffeoylguinic acid : antioxidant, anti-hyaluro-nidasic, anti-collagenasic activity - Phytosterols, amino acids, polysaccharides : moisturizing and nutrients

Currently, apple stem cell technology is popping up

everywhere for beauty use

For Health An Apple a Day Keeps the Doctor

Away

For BeautyAn Apple a Day Keeps the Wrinkles

Away

- Apple Stem Cells as Anti Aging Ingredient

- The current find is a rare Swi ss apple, called the Uttwiler S

patlauber , which actually hea ls itself when punctured

- The rare Swiss apple has a re newal power that rejuvenates saggy skin

- Apple stem cells help boost t he production of human skin s

tem cells by protecting skin fr om stress and decreasing fine

lines and wrinkles

From Uttwiler Spätlauber, the “super apple” with the aid of modern plant stem cell technology

Selecting / taking away a small piece of the plant

Wounding of plant material to induce callus formation

Incubation on agar plates

Harvesting of the developed callus

Cultivation until complete dedifferentiation to obtain stem cells

Transfer of the stem cells into liquid media for growing

Disruption of the stem cell wall to release secondary metabolites

Encapsulation of the stem cell contents into liposome

Fixing in xanthan gum gel

- Based on an extract of cultured apple stem cells- Formulated with nanotechnology that allows a higher encapsulation in a smaller molecule- Allows better penetration to deliver deep into the skin- Minimizes trans epidermal water loss- Enhances new stem cell production- Protect against stem cells from UV- Released by skin heat (33oC) when is applied

Encapsulated nano-emulsion PhytoCellTecstem cell cream before touching the skin

Heat activated release of PhytoCellTec stem cell cream after touching the skin

Potentials of Malus domestica stem cell extract in increasing the number of human umbilical cord stem cells

Potentials of Malus domestica stem cell extract in protecting human umbilical cord stem cells from the impact of UV

Skin stem cell activity

Before PhytoCellTecTM treatment 1-h after PhytoCellTecTM treatment

- Won the 2008 innovation prize for best active ingredient in Europe- The reason it won is because its revolutionary of stem cell technology and its ability to harness the regenerative potential of own facial stem cells to renew skin (make it look young again)

Cosmetic Use

> Protect skin stem cells> Increase activity of skin stem cells> Decrease of senescence markers in fibroblasts> Maintain the power of skin cell regeneration> Decrease in wrinkles

Potentials of Malus domestica stem cell extract on reducing of skin

wrinkles

55 years old

Week 1 Week 2 Week 3 Week 4

Korean Ginseng

A medicinal herb with miraculous virtue in the high mountains and secluded valleys

A first record of prescription of ginseng as a medicinal herb appeared in Shen-Neng Pharmacopeia (AD 456-536)

During the Koryo Dynasty (AD 918-1392), ginseng was renowned as the best medicine with miraculous potency It was called a miraculous medicine, a cure-all and believed to be a miraculous medicine, a source of eternal youth

From 100 years old Wild Korean Ginseng (rare to find, even in deep mountains) with tissue culture technology

Non-GMO : no genetic modificationSafety : animal free, no-infectionEco-friendly : no extraction, no pollutionNo metals : no heavy metal sourcesPesticide free : no pesticide neededFast growth : no need to wait 100 years for wild ginsengTechnology : tissue culture, nano-liposomeLow cost : low production cost

Genetic similarity by AFLP fingerprinting

Cosmetic Use

Collagen synthesis Cell proliferation Photo-protection Antioxidant Whitening

Contains high biological substances - Saponins called “ginsenosides” : protopana-xadiol, triol and pleanolic acid - Carbyhydrates : oligo- and polysaccharides, fiber, pectine - Lipid soluble component : fat, phytosterol, essential oils, terpenoids, organic acids - Nitrogenous compounds : Amino acids, peptide, protein, alkaloid, nucleic acid - Vitamins & minerals

Oh My God Perfect Gel Japan

IOPE Plant Stem Cell Skin Renewal Serum Korea

Bielenda In Vitro Roslinne Komorki Macierzvste Anti-Age Day Cream SPF 10

Poland

éclos Anti-Aging Facial Cleanser Skin Prep USA

Rampal Latour en Provence Geneviève PatouShampoo & Shower Gel Sweet Almond - Sage Bergamot

France

Crescina Stem Forte Re-Growth Italy

IOPE Plant Stem Cell Skin Renewal Serum

IOPE's cutting edge technology brings an innovative anti-aging skin care line . Plant stem cells

are the source of unlimited e nergy and the key to herbal

growth and regeneration

Bielenda In Vitro Roslinne Komorki Macierzvste Anti-Age Day Cream SPF

10Effectively repairs age-related skin damage, restores the skin's firmness and smoothness, reduces deep wrinkles, furrows and mimic lines, provides intensive hydration and protects the skin against excessive water loss, whilst restoring elasticity and glow and improving the skin's suppleness and density with its lifting effect .Formulated with a plant stem cells that naturally regenerate and renew, protect skin stem cells against ageing by delivering nutrients essential for the formation of new, young cells . The stem cells stimulate the production of collagen, reduce wrinkles and recover the skin's firmness and youth .

éclos Anti-Aging Facial Cleanser Skin Prep Contains high potency plant stem cells for cellular rejuvenation. To extend skin cell longevity, cleanse deep down, and gently purify pores. Clinical results give a 100% reported decrease in wrinkle depth due to the product's tremendous ability to stimulate skin stem cells, encouraging aging skin to behave in a more youthful way.

Lancôme Définicils Precious Cells Mascara

- Contains the apple extract blended with proteins and lipids for a deeply hydrating experience- The potential in stimulating the growth and health of lashes

Plant stem cells : ♥ are natural and free from many unwanted issues e.g., GMO, environmental contaminants ♥ contains substances that can be beneficial for human health and beauty ♥ Can be produced by modern technology and encapsulated for better properties ♥ Are compatible to human skin and support skin stem cells as well as help protect the skin from environmental stress ♥ are now available as the cosmetic ingredients in the market ♥ have been used worldwide in skin care and make up products

Sunee ChongcharoenchitSiriluk SreepanMerck (Thailand) Ltd. P.C. Intertrade Co., Ltd Chemico Inter Corporation Co., Ltd Croda Singapore PTE Ltd (Thailand Representative Office)