Current Research and Product Development

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???????????????? ?????? Plant Stem Cell in
Cosmetics
August 25, 2010
Current Research and Product Development Using
Plant Stem Cells
Malyn Chulasiri BSPharm, PhD Director, Research
Development, SJI Professor Emerita, Faculty of
Pharmacy, Mahidol University
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I Cant Believe The Hype Beauty Products With
Plant Stem Cells by Aaron Saenz on June 30th, 2010
- 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 were so enraptured with
the possibility of human stem cell technologies
that well buy anything with stem cells in the
product name?
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Stem Cells

• - 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

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Animal Stem Cells
? 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
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Animal Stem 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
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Skin Stem Cells
Normal
Without C/EBP-beta
Differntiated cells
Stem cells
Stem cells
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Stem Cells in Skin

• ? 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 production
• A loss is detrimental to the skin (one ages skin
  stem cell division diminishes dramatically
  causing in wrinkles and thinned skin)

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Plant Stem Cells
? 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
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Plant Stem Cells Formation of Callus Tissue
? 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)
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Stem cells can make identical copies of
themselves as well as generate specialized cells
Day 2 Day 3
Day 6
Stem cells grown into filamants
Stem cells
Stem cells
Progenitor cell (stem cell)
Development into protonemal colony
Dead cells
Transient amplifying cell
Differentiated cell
Reprogramming of P. patens leaflet cells
into stem cells and subsequent protonemata
development
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Growth Enhancing Hormones Auxins
Why Plant Stem Cells for Human Use?

• - Have 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
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Plant Stem Cells A New Ingredient for Health
Beauty
? 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 ones needs ? Safe for both
cosmetic and nutritional applications
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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
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Plant Stem Cells Utilized Parts as Ingredients
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Plant Stem Cells Versus Human Skin (for Beauty)
? 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
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Marketed Plant Stem Cells for Cosmetics
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
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Stem Cells for Cosmetics from Flower Plants
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
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Stem Cells for Cosmetics from Fruit Plants
Malus Domestica Preserve the youthful look and the vitality of skin
Vitis Vinifera Protect skin stem cells against UV stress, fight photoaging
Stem Cells for Cosmetics from More Kinds of
Plants
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
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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
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Example of Marketed Edelweiss Stem Cells for
Cosmetics Use Leontopodium Alpinum Stems G
From Edelweiss, the symbol of Alpine flora with
the aid of High Tech Nature (HTN) biotechnologoy
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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
Callus
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Cosmetics with Ingredient from Edelweiss Stem
Cell Ingredient
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
Cosmetic Use
gt Reduction of eye contour wrinkle gt
Prevention of collagen loss gt Firming and
restructuring treatments gt Prevention of
aging and photo-aging
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Edelweiss Stem Cell Treatment
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For Health An Apple a Day Keeps the Doctor Away
For BeautyAn Apple a Day Keeps the Wrinkles
Away
Currently, apple stem cell technology is popping
up everywhere for beauty use
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Apple Stem Cells as Anti-Aging Ingredient
- The current find is a rare Swiss apple, called
the Uttwiler Spatlauber, which actually heals
itself when punctured - The rare Swiss apple has
a renewal power that rejuvenates saggy skin -
Apple stem cells help boost the production of
human skin stem cells by protecting skin from
stress and decreasing fine lines and wrinkles
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Example of Marketed Apple Stem Cells for
Cosmetics Use PhytoCellTec Malus Domestica
From Uttwiler Spätlauber, the super apple with
the aid of modern plant stem cell technology
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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
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- 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
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Encapsulated nano-emulsion PhytoCellTecstem
cell cream before touching the skin
Heat activated release of PhytoCellTec stem
cell cream after touching the skin
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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
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Skin stem cell activity
Before PhytoCellTecTM treatment 1-h
after PhytoCellTecTM treatment
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- 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)
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Cosmetic Use gt
Protect skin stem cells gt Increase activity of
skin stem cells gt Decrease of senescence markers
in fibroblasts gt Maintain the power of skin cell
regeneration gt Decrease in wrinkles
Cosmetics with Ingredient from Apple Stem Cells
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55 years old
Apple Stem Cell Cosmetic Treatment
Week 1 Week 2
Week 3 Week 4
Potentials of Malus domestica stem cell extract
on reducing of skin wrinkles
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• 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

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Example of Marketed Ginseng Stem Cells for
Cosmetics Use Actostem WKGBASE
From 100 years old Wild Korean Ginseng (rare to
find, even in deep mountains) with tissue culture
technology
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Plant Tissue Culture
Non-GMO no genetic modification Safety animal
free, no-infection Eco-friendly no extraction,
no pollution No metals no heavy metal
sources Pesticide free no pesticide needed Fast
growth no need to wait 100 years for wild
ginseng Technology tissue culture,
nano-liposome Low cost low production cost
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Genetic similarity by AFLP fingerprinting
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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
Cosmetics with Ingredient from Ginseng Stem Cells
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Descriptions of Some Cosmetics with
Ingredients from Plant Stem Cells
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Skin Care Products
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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
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éclos Anti-Aging Facial Cleanser Skin Prep USA
Rampal Latour en Provence Geneviève Patou Shampoo Shower Gel Sweet Almond - Sage Bergamot France
Crescina Stem Forte Re-Growth Italy
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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 energy and the
key to herbal growth and regeneration
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Bielenda In Vitro Roslinne Komorki Macierzvste
Anti-Age Day Cream SPF 10
Effectively 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.
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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.
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Makeup Products
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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
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Conclusion
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
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ACKNOWLEDGEMENTS
Sunee Chongcharoenchit Siriluk Sreepan Merck
(Thailand) Ltd. P.C. Intertrade Co., Ltd
Chemico Inter Corporation Co., Ltd Croda
Singapore PTE Ltd (Thailand Representative Office)