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MossCellTec™ No. 1 Enhances cell nucleus function for resilient skin
MossCellTec™ No. 1Enhances cell nucleus function for resilient skin
Moss Tissue Culture to Improve Cell Nucleus Health and Fortify the SkinWith MossCellTec™ No. 1, Mibelle Biochemistry offers an anti-aging treatment that is based on a novel concept: cell nucleus health.
MossCellTec™ No. 1 supports cell nucleus health by improving the expression of protein markers that:• structure the nuclear envelope • enable the efficient transport of molecules into and
out of the nucleus. Together, both allow for a proper communication between the nucleus and cytoplasm, which is essential for the cell functioning. However, they are impaired by aging. Therefore, preserving the cell nucleus health represents a novel strategy in the fight against aging.
MossCellTec™ No. 1 has been developed from an extract of the cells of the Physcomitrella patens moss. It is the first active ingredient on the market that is based on bio technologically produced moss which is obtained in a reproducible and sustainable way by tissue culture. Mosses are among the first land plants to conquer the earth. Their extremely high resilience to a changing environment makes them of considerable interest in re-gard to fortifying our skin.
In vitro and clinical studies have shown that MossCellTec™ No. 1 helps the skin to adapt to fast climatic changes. This results in a significant increase in skin hydration, homo-geneity and barrier function despite changing climatic conditions in just two weeks, as well as a reduction in wrinkle depth after just four weeks.
Therefore, by maintaining an efficient transport of the molecules into and out of the nucleus and by preserving the organization of the nuclear envelope, the commu-nication inside the cell is optimized and cells can adapt more quickly to the ever-changing environment, making our skin more resilient.
MossCellTec™ No. 1 is COSMOS approved *.
MossCellTec™ No. 1• Enables skin to adapt to environmental changes • Improves skin moisture, even in stressful conditions • Refines skin and creates a flawless complexion • Maintains cell nucleus health to ensure youthful skin • Strengthens skin resilience against urban aggressors
Applications• Anti-aging treatments • Formulations for all types of weather • Protection and repair formulas• Moisturizing skin care
Formulating with MossCellTec™ No. 1• Recommended use level: 2 %• Incorporation: For cold processes, dissolve
MossCellTec™ No. 1 into the aqueous phase. In hot / cold processes, add during the cooling phase below 40 °C.
• Thermostability: Temperatures of up to 40 °C for a short time will not affect the stability of MossCellTec™ No. 1.
INCI (EU / PCPC) DeclarationPhytol (and) Isomalt (and) Aqua / Water
Additional Information• Not preserved• Alcohol-free
MossCellTec™ No. 1Enhances cell nucleus function for resilient skin
February 2019
* Raw material approved by ECOCERT GREENLIFE in accordance with the COSMOS Standard
The Pioneer Plants that Actively Built the SoilMosses, which belong to the Bryophyte group, are among the first land plants to have conquered the earth approximately 470 million years ago (1). These pioneer organisms can be found virtually all over the world.
Mosses contribute to the building and structure of the ground, prevent erosion and provide humus for other plants such as trees to flourish. They also offer a habitat to a variety of small organisms.
Furthermore, mosses are able to trap excess water and nutrients from the soil, air and rain by acting like a sponge. Mosses can rapidly absorb water from the atmo sphere in a consistent way (up to 20 times their weight). Meanwhile, in dry weather, mosses gradually restore the rainwater and in doing so increase the humidity and cool down the air.
The Plants that Best Resist the Lack of Water Mosses neither have roots nor a vascular system that allow for the transportation and storage of water and nutrients. These compounds are absorbed by imbibi- tion and diffusion through the numerous and ultrathin leaves of the moss.
Mosses are able to tolerate long periods of desiccation where they stop their metabolism (dormant phase) thanks to metabolites that retain water. When water is available again, mosses can rehydrate in just a few minutes and return to a normal life (revivis-cence phenomenon).
MossesExtraordinarily resilient to environmental changes
Mosses Can Be Found Virtually All Over the World
High Tolerance to Freezing thanks to “Cold Genes”Mosses have leaves that consist of a singular cell layer which means that every single cell is exposed to and must handle the environmental stresses.
Unlike higher plants, mosses are able to survive several freeze-thawing cycles. Indeed, despite being frozen under hundreds of meters of ice for over 1,500 years they are still alive (2)! This extraordinary resilience is due to the presence of “cold genes” that are unique to mosses and which turn on as soon as the temperature drops (3).
High Tolerance to Pollutants thanks to AntioxidantsMosses filter all of the necessary nutrients from the air and rain but they also accumulate air pollution particles such as heavy metals, polycyclic aromatic hydrocarbons (PAHs) and dioxins. This ability to actively filter the air has been exploited to monitor the level of air pollution over the years.
In order not to poison themselves and to protect from the heavy metals, mosses have a large set of antioxidants to mitigate the effects of accumulating toxic compounds.
Notably, this high resilience to environmental changes explains why mosses were able to adapt quickly enough to climate changes and survive from the prehistoric times to today.
1. First plants cooled the Ordovician, Crouch et al., Nature Geoscience · February 20122. Millennial timescale regeneration in a moss from Antarctica, Roads et al., Current Biology 24(6):R222-3 (2014)3. Insights from the cold transcriptome of Physcomitrella patens: global specialization pattern of conserved transcriptional regulators
and identification of orphan genes involved in cold acclimation, Beike et al., New Phytologist (2015) 205: 869–8814. Rote Liste der gefährdeten Moose der Schweiz, Schnyder et al., BUWAL – Bundesamt für Umwelt, Wald und Landschaft, Bern Ausgabe 20045. Quantitative determination of nuclear pore complexes in cycling cells with differing DNA content, GG Maul et al., JCB. 1977; 73(3): 7486. Kinetic analysis of translocation through nuclear pore complexes, Ribbeck et al., EMBO J. 2001; 20(6): 1320 -13307. Lost in Transportation: Nucleocytoplasmic Transport Defects in ALS and Other Neurodegenerative Diseases, Kim et al.,
Neuron. 2017; 96(2): 285-297
Protonema Stage of P. patens
A Source of Interest that is yet to be ExploitedIn Traditional Chinese Medicine, more than forty species of bryophytes are used, for example topically, in order to reduce either inflammation or the pain of insect bites. However, until now, mosses did not raise much aware-ness from the cosmetic field mainly because:• they don’t have flowers and are often considered as
something to eliminate in gardening• they have no relevance as a foodstuff, neither for
humans nor animals.
Several Drawbacks to Face in order to Access MossesMosses are difficult to collect in a sustainable way because:• they grow slowly, are often crucial parts of an eco-
system and some species are already suffering from extinction due to the increasing use of land (such as, for example the approximately 38 % of the more than 1,000 moss species in Switzerland (4))
• they are difficult to identify and therefore harvesting from nature would result in mixed species being collected
• mosses may contain toxins and would therefore need to be purified
• whilst cultivation in greenhouses is possible, this would require a lot of land and water.
MossCellTec™ Enables the Cell Culture of Mosses in a Sustainable and Reproducible Way MossCellTec™ is a novel technology that, for the first time, enables the large scale cultivation of moss cells in sterile conditions and in both a reproducible and sustain-able way. Indeed, this process requires a small quantity of plant material just once.
This technology is based on the capacity of moss cells to divide after the fragmentation of its leaves (asexual reproduction).Cells from the Physcomitrella patens moss were harvested and cultivated in the protonema stage (germinating spore). For the first time, a large scale production could be established.Finally, in order to obtain the MossCellTec™ No. 1 cosmetic ingredient, the resulting extract was carefully sprayed on a powder based on isomalt.
Other Advantages of MossCellTec™ TechnologyThis technology offers these additional advantages:• availability of plant material regardless of the
season and market demand• plant material that is completely free of environmental
pollutants and pesticides.
MossCellTec™ Acquiring pure moss in a sustainable and reproducible way
Cells with Nuclei The Nucleus
The Nuclear EnvelopeMore than just a protective barrier for DNA
The Nuclear Envelope Separates the Nucleus from the Cytoplasm Present in all of our cells, the nucleus contains and protects DNA, which is the blueprint for all activities in the cells.
The nucleus is surrounded by an envelope which is per-forated by pores formed by the nuclear pore complex. These pores allows:• the export of transcribed messenger RNAs (mRNAs)
from the nucleus to the cytoplasm, where translation will take place
• the selective and bidirectional transport of many different macromolecules, such as transcription factors.
This flow of molecules makes the communication between the nucleus and the cytoplasm possible and is essential for the cell, to know, when to divide and how to respond to environmental stimuli, as well as how to adapt to them. This traffic into and out of the nucleus is also essential to preserving the organization and functioning of the cell.
Smaller molecules (< 40 kDa) simply diffuse (passively) through the pores and larger ones such as proteins and mRNA need the help of specific transport proteins to convey into or out of the nucleus.
This transport process is highly complex: In a single human cell, there can be up to 5,000 nuclear pores and each can transport 1,000 molecules per second (5,6). This means that in one cell, up to 5 million molecules are transported into and out of the nucleus every second.
Nuclear pore complex
Nuclear envelope
Nucleus
Cytoplasm
Transport of proteins and mRNA
DNA
Cell Nucleus HealthA novel anti-aging concept
The Transport of Molecules into and out of the Nucleus
Age Disturbs the Nuclear TransportWith age, the efficiency and selectivity of the transport of molecules through the nuclear pores decrease (7).Recent studies have shown that RanBP17 (Ran-binding protein-17), which is a transport protein that enables and controls the flow of molecules through the nuclear pore, is reduced with age in several cell types, including fibroblasts and neurons. It was also shown that this decrease influenced various important aging processes. This highlights the crucial role of RanBP17 and the nuclear transport process in aging regulation.
Age Impairs the Nuclear EnvelopeWith aging, the expression of lamin A is reduced. This protein confers mechanical support (structure, stiffness and resistance to deformation) to the nuclear membrane, maintains the shape of the nucleus and plays a role in several cellular processes. In subjects who suffer from the premature aging syndrome Hutchinson-Gilford progeria (HGPS), lamin A is mutated and is therefore not correctly processed. The resulting truncated lamin (progerin) leads to nucleus deformation and accelerated aging. This demonstrates a link between lamin A and aging.
Mechanism of MossCellTec™ No. 1MossCellTec™ No. 1 was shown to improve the expression of important cell nucleus health markers involved in the nuclear envelope structure and transport into and out of the nucleus in aged cells.
In vitro and clinical studies showed that MossCellTec™ No. 1 helps the skin to adapt to fast climatic changes (cold / hot, low / high relative humidity). This results in a significant increase in skin hydration, homogeneity and barrier function despite changing climatic conditions in just two weeks, as well as a reduction in wrinkle depth after just four weeks.
Therefore, by maintaining an efficient transport of the molecules into and out of the nucleus and by preserving the organization of the nuclear envelope, the commu-nication inside the cell is optimized and cells can adapt more quickly to the ever-changing environment, making our skin more resilient.
Aging
MossCellTec™ No. 1
Young cell Old cell
Protein
mRNA
Impaired stability of the envelopeReduced transport of proteins and mRNA into and out of the cell nucleus
aging processes slow adaptation to changes
Well-organized transport into and out of the cellResistant and well-structured envelope
fast production of new metabolites quick adaptation to a changing environment
MossCellTec™ No. 1Study results
Nuclear Structure and Transport Proteins Protection of Cell Nucleus Health Markers
Protection of the Cell Nucleus from AgingThe ability of MossCellTec™ No. 1 to protect the structure and activities of the cell nucleus
from aging was evaluated by measuring its effect on several genes that were selected for their important role in the nuclear structure and the transport of molecules through the nuclear pores.
Firstly, the expression of these genes was analyzed using quantitative PCR on normal human epidermal kera - t inocytes that were isolated from both a young donor (a 20 year old woman) and an older donor (a 55 year old woman).
Secondly, the keratinocytes from the older donor were either treated or not (control) with different concentrations of the P. patens extract (for 24 hours). From there, the expression of the genes previously defined was analyzed using quantitative PCR.
Results showed that the expression of the three following genes was decreased in the “older keratinocytes” com-pared to the younger ones:• LMNA gene that codes for the lamin A structural
protein, a component of the lamina • TMPO gene that codes for the LAP2 protein, which
plays a role in the assembly of the nuclear lamina • RANBP17 gene that codes for the Ran-binding
protein-17 (RanBP17), which is a nuclear transport receptor.
However, treatment with P. patens extract resulted in an increased expression of these three specific genes in a concentration-dependent manner. Therefore, P. patens extract exerts a rejuvenating effect as regards cell nucleus genes and preserves the structure and activities of the cell nucleus despite aging.
Nuclear pore complex
LAP2 (envelope protein)
Lamin A (envelope protein)
Nucleus
RanBP17 (transport protein)
Protein
Nuclear envelope
Gen
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pre
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mp
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youn
g c
ells
(=10
0) in
%
Control 0.33 % P. Patens extract 1 % P. Patens extract
RanBP17
Young cells Old cells
LAP2 Lamin A
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40
20
120
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MossCellTec™ No. 1Study results
Reinforcement of the Skin Barrier QualityThe ability of MossCellTec™ No. 1 to reinforce the skin barrier was evaluated by measuring
its effect on several genes that were selected for their important role in skin barrier function, epidermal matrix and hydration.
The expression of these genes was analyzed using quantitative PCR on normal human epidermal kera- t inocytes that were first either treated or not (control) with the P. patens extract.
Results showed that the P. patens extract increased the expression of two important groups of genes:• genes that encode the proteins forming the stratum
corneum: involucrin, filaggrin, repetin and small proline-rich (SPRR) proteins
• genes that encode the proteins that form junctions between the cells such as desmosomes (envoplakin, corneodesmosin, desmoglein 1) and tight junctions (F11 receptor).
By stimulating filaggrin, the P. patens extract increases the capacity of the skin to trap and hold water.
Furthermore, the P. patens extract limits water loss by increasing the gene expression of the constituents of the stratum corneum.
Last but not least, the P. patens extract reinforces the cohesion between the cells by increasing the gene expression of the constituents of desmosomes and tight junctions. The latter control the diffusion of water and solutes across intercellular spaces and therefore prevents loss of water.
Stimulation of Skin Barrier Markers
250
200
150
100
50
0
Gen
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=10
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F11Receptor
Envoplakin Desmoglein 1Corneo-desmosin
SPRR1A SPRR1BRepetin
Proteins forming the stratum corneum Desmosomes Tightjunctions
Filaggrin Involucrin
1 % P. Patens extract
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Improved Adaptability to Repeated Short Climatic StressThe protective effect of MossCellTec™ No. 1
against climatic variations (temperature and humidity level) was evaluated by using a reconstructed skin model. Several parameters were studied in terms of skin structure and biological response.
The reconstructed skin was treated with 1 % MossCellTec™ No. 1. From there, short daily climatic stresses were applied in order to replicate transient exposure to either summer conditions (hot and humid: 40 °C, 80 % rela- tive humidity) for 30 minutes, 3 times over a period of 36 hours or external winter conditions (cold and dry: 10 °C, 40 % relative humidity) for 15 minutes, 3 times over a period of 36 hours.
Hematoxylin-eosin staining showed that climatic stress, especially cold and dry weather, induced damages in the 3D skin and notably disorganized the fibers of the dermal matrix. However, pre-treatment with MossCellTec™ No. 1 could prevent these changes as the structural morphology of the 3D skin remained unchanged com-pared to the un treated control. Therefore, thanks to MossCellTec™ No. 1, the skin cells were able to adapt more efficiently to these climatic stresses.
Protection against the Damages Induced by Extreme Temperature and Humidity Conditions
Normal conditions
Con
trol
1 %
Mos
sCel
lTec
™ N
o. 1
Hot and humid
Collapseddermal structure
Cold and dry
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MossCellTec™ No. 1Study results
Adaptation to Climatic StressImmunostaining showed an increased expres-sion of LCE1A, which is a stress marker that
is activated in case of temperature changes, especially when the climate is hot and humid. However, pre-treat-ment with MossCellTec™ No. 1 was shown to inhibit this effect, which indicates a prevention of the stress.
In addition, the stratum corneum thickness was also quantified in pixels.• Pre-treatment with MossCellTec™ No. 1 was shown
to increase the stratum corneum thickness by almost 15 %.
• In addition, while cold and dry stress led to a 47 % reduction of the stratum corneum thickness compared to initial conditions, treatment with MossCellTec™ No. 1 was shown to limit this decrease to less than 10 % and therefore help the skin to adapt more quickly and effectively to cold weather (data not shown).
Inhibition of LCE1A (Stress Marker) Activation
Normal conditions
Hot and humid
Rela
tive
LCE1
A c
onte
nt c
omp
ared
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cont
rol c
ells
in n
orm
al c
ond
ition
s (=
1)
Control 1 % MossCellTec™ No.1
Normal conditions
**
*
*
Hot and humid Cold and dry
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*p<0.05 versus control (normal conditions) **p<0.05 versus control (hot and humid)
0
5
15
10
blue = cell nuclei (DAPI)
red = LCE1AS-713 / © Mibelle Biochemistry
Improvement of the Skin BarrierFifteen Caucasian women aged between 37.4 and 64.7 years (mean age: 52.7 years) applied
either a cream with 2 % MossCellTec™ No. 1 on the inner side of their forearm or the corresponding placebo on the other inner side of their forearm twice daily for a period of 28 days. The TEWL was determined by using a tewameter.
Treatment with MossCellTec™ No. 1 led to an average decrease in TEWL of almost 8 % compared to the placebo (up to 20 %). The TEWL of the skin was decreased for 73 % of the volunteers.
During this study, high resolution pictures were taken using Visioscan® in order to visualize the structure of the skin surface and the level of dryness. Pictures taken before the treatment showed numerous signs of scaliness. However, treatment with MossCellTec™ No. 1 led to the complete disappearance of these signs of dryness (data not shown).
Anti-Wrinkle EffectFourteen Caucasian women aged between 37.4 and 65.4 years (mean age: 53.7 years)
applied either a cream with 2 % MossCellTec™ No. 1 on one half of their face or the corresponding placebo on the other half of their face twice daily for a period of 28 days.
The wrinkle depth of the crow’s feet area was determined by using the PRIMOS system.
Treatment with MossCellTec™ No. 1 led to an average de-crease in wrinkle depth of 15 % compared to the placebo.
Decrease in TEWL Anti-Wrinkle Effect on Crow’s Feet
Dec
reas
e in
TEW
Lco
mp
ared
to
initi
al c
ond
ition
s in
%
Placebo 2 % MossCellTec™ No.1
*
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*p<0.05 versus initial conditions and placebo
0
8
6
4
2
10
Dec
reas
e in
wrin
kle
dep
thco
mp
ared
to
initi
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ond
ition
s in
%
Placebo 2 % MossCellTec™ No.1
*
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*p<0.05 versus initial conditions
0
15
10
5
20
MossCellTec™ No. 1Study results
Improved Adaptability to Climatic StressTwenty-three women aged between 39 and 53 years (mean age: 45.4 years) applied either a
cream with 2 % MossCellTec™ No. 1 on one half of their face or the corresponding placebo on the other half of their face twice daily for 14 days. • Volunteers spent 2 – 5 hours per day outdoors. • The study took place during the summer in Seoul,
South Korea.• The skin of the volunteers had to adapt to sudden
changes between hot and humid weather outside and air conditioning inside.
• One week before starting, each volunteer only applied the placebo cream twice daily on their entire face.
The hydration and the TEWL were determined on the cheeks of the volunteers by using a corneometer and a vapometer respectively.
The homogeneity of the skin color was analyzed by taking cross-polarized images using VISIA® CR and by calcu lating the standard deviation of each of the pixels. The higher the standard deviation, the higher was the heterogeneity of the complexion.
Overall Improvement of the Skin Aspect despite Climatic Changes
10
8
6
4
2
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-2
Cha
nge
com
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ed t
o in
itial
con
diti
ons
in %
Decrease in TEWL Increase in skin color homogeneityIncrease in hydration
Day 7 Day 7 Day 7Day 14 Day 14 Day 14
Placebo 2 % MossCellTec™ No.1
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**
*
****
**
**
*p<0.05 versus initial conditions**p<0.05 versus initial conditions and placebo
Treatment with MossCellTec™ No. 1 led to a significant increase in hydration and decrease in TEWL from the first week of application:• skin hydration was increased by more than 6 % after
two weeks compared to initial conditions (up to 17.5 %). The hydration of the skin was increased for 100 % of the volunteers.
• TEWL was reduced by more than 8 % after two weeks compared to initial conditions (up to 20 %). The TEWL of the skin was decreased for 91 % of the volunteers.
In addition, MossCellTec™ No. 1 significantly and visibly improved the homogeneity of the skin color after a two week treatment. Indeed, the pictures below clearly show that the heterogeneity of the skin color was reduced following the treatment.
Therefore, MossCellTec™ No. 1 helps the skin to quickly adapt to environmental changes.
Visible Improvement of the Skin Aspect despite Climatic Changes
Before After 2 weeks
S-709 / © Mibelle Biochemistry
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MossCellTec™ No. 1Enhances cell nucleus function for resilient skin
The information contained in this publication is provided in good faith and is based on our current knowledge. No legally binding promise or warranty regarding the suitability of our products for any specific use is made. Any statements are offered solely for your consideration, investigation and verification and do not relieve you from your obligation to comply with all applicable laws and regulations and to observe all third party intellectual prop-erty rights. Mibelle AG Biochemistry will not assume any expressed or implied liability in connection with any use of this information and disclaims any and all liability in connection with your product or its use. No part of this publication may be reproduced in any manner without the prior written permission of Mibelle AG Biochemistry.
MossCellTec™ No. 1• Enables skin to adapt to environmental changes • Improves skin moisture, even in stressful conditions • Refines skin and creates a flawless complexion • Maintains cell nucleus health to ensure youthful skin • Strengthens skin resilience against urban aggressors
Applications• Anti-aging treatments • Formulations for all types of weather• Protection and repair formulas• Moisturizing skin care
Marketing Benefits• Four time awarded active ingredient:
Gold Award at Innovation Zone Best Ingredient Award in-cosmetics Global Gold Award at BSB Innovation Prize 3rd Prize at Sepawa Innovation Prize Gold Award at Innovation Zone Best Ingredient in-cosmetics North America
• First active ingredient on the market that is based on biotechnologically produced moss which is obtained in a reproducible and sustainable way
• New anti-aging concept based on cell nucleus health• Not preserved • COSMOS approved
Innovating for your successMibelle Biochemistry designs and develops innovative, high-quality actives based on naturally derived compounds and profound scientific know-how. Inspired by nature – Realized by science.
