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Academic articles of Stem Cell Conditioned Medium
in Anti-aging Skin care
www.silkah.com
email: info@silkah.com
Ref. 1
Source: Textbook of Aging skin, P. 209, Figure 20.10
Objective and subjective evaluation of the protein extracts from ADSC-CM in a large-scale (n= 235)
pilot study in terms of: (a) winkles, (b) acquired pigmentary lesions, and (c) dilated pores. The
evaluation score is based upon the following scales: 0= poor/ worsened; 1= no change; 2= fair/ mild
improvement; 3= good/ moderate improvement; 4= excellent/ marked improvement. As compared to
47.4% showing good to excellent improvement in wrinkle (a), 63% of the patients were judged
to have good to excellent improvement in acquired pigmentary lesions (b) and dilated pores (c).
Ref. 2
Source: 2008.oct. Dermatol Surg; 34(10): P. 1323-6
Adipose-derived stem cells and their secretory factors as a promising therapy for skin aging.
Adipose-derived stem cells (ADSCs) and their secretory factors can stimulate collagen
synthesis and migration of fibroblasts during the wound healing process. Conventional treatments
for skin aging, such as lasers and topical regimens, induce new collagen synthesis via activation of
dermal fibroblasts or growth factors. Considering the results of our previous study, ADSCs can also
be used for the treatment of skin aging.
We demonstrated that ADSCs produce many useful growth factors, increase collagen production
in animal study, and reverse skin aging in human trial.
ADSCs and their secretory factors show promise for application in cosmetic dermatology,
especially in the treatment of skin aging.
Ref.3
2008.April, Biol Pharm Bull.; 31(4): P. 606-10
Whitening effect of adipose-derived stem cells: a critical role of TGF-beta 1.
It has been demonstrated that adipose-derived stem cells (ADSCs) secrete cytokines and
exhibit diverse pharmacological actions. The present study examined the unknown pharmacological
action of ADSCs regarding whitening effects. ADSC-CM treatment inhibited the synthesis of melanin
and the activity of tyrosinase in a dose dependent manner. Transforming growth factor-beta1 (TGF-
beta 1), a potent regulator of melanogenic proteins, was neutralized by the addition of a blocking
antibody to ADSC-CM, and down-regulated expression of tyrosinase and TRP1 was almost reversed.
Collectively, these results indicate that secretary factors of ADSC inhibit melanin synthesis by
down-regulating the expression of tyrosinase and TRP1, which are mainly mediated by TGF-
beta1.
Ref. 4
2008,April. PLoS One.; 3(4): P. e1886
Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells
and enhance wound healing.
Bone marrow derived mesenchymal stem cells (BM-MSCs) have been shown to enhance wound
healing; however, the mechanisms involved are barely understood. In this study, we examined
paracrine factors released by BM-MSCs and their effects on the cells participating in wound healing
compared to those released by dermal fibroblasts. BM-MSC-conditioned medium significantly
enhanced migration of macrophages, keratinocytes and endothelial cells and proliferation of
keratinocytes and endothelial cells compared to fibroblast-conditioned medium. Moreover, in a mouse
model of excisional wound healing, where concentrated BM-MSC-conditioned medium was applied,
accelerated wound healing occurred compared to administration of pre-conditioned or fibroblast-
conditioned medium. Our results suggest that factors released by BM-MSCs recruit macrophages
and endothelial lineage cells into the wound thus enhancing wound healing.
Ref. 5
2009, Feb., J Dermatol Sci.期刊; 53(2): P. 96-102
Antiwrinkle effect of adipose-derived stem cell: activation of dermal fibroblast by secretory
factors.
Adipose-derived stem cells (ADSC) have wound-healing and antioxidant effects on human skin
via secretion of growth factors and activation of dermal fibroblasts. Paracrine mechanism reducing
ultraviolet-B (UVB)-induced wrinkles by ADSC is investigated in this study.
To characterize the paracrine mechanism involving the antiwrinkle effect of ADSC, a conditioned
medium of ADSC (ADSC-CM) was directly incubated in human dermal fibroblasts (HDF). UVB
irradiation reduced the proliferation of HDF, but this was reversed by the pretreatment of ADSC-CM
in a dose-dependent manner. In addition, the ADSC-CM increased the protein expression of collagen
type I and decreased the protein level of matrix metalloproteinase 1 in HDF, which may account for
the increased collagen contents in the dermis.
Collectively, these results indicate that the ADSC and its secretory factors are effective for
UVB-induced wrinkles, and the antiwrinkle effect is mainly mediated by reducing UVB-induced
apoptosis and stimulating collagen synthesis of HDF.
Ref. 6
Stem Cell Res Ther. 2015 Aug 18;6:145.
Intralesional injection of adipose-derived stem cells reduces hypertrophic scarring in
a rabbit ear model.
Abstract
INTRODUCTION:
Redundant collagen deposition at sites of healing dermal wounds results in hypertrophic
scars. Adipose-derived stem cells (ADSCs) exhibit promise in a variety of anti-fibrosis
applications by attenuating collagen deposition. The objective of this study was to explore the
influence of an intralesional injection of ADSCs on hypertrophic scar formation by using an
established rabbit ear model.
METHODS:
Twelve New Zealand albino rabbits were equally divided into three groups, and six identical
punch defects were made on each ear. On postoperative day 14 when all wounds were
completely re-epithelialized, the first group received an intralesional injection of ADSCs on
their right ears and Dulbecco's modified Eagle's medium (DMEM) on their left ears as an
internal control. Rabbits in the second group were injected with conditioned medium of the
ADSCs (ADSCs-CM) on their right ears and DMEM on their left ears as an internal control.
Right ears of the third group remained untreated, and left ears received DMEM. We quantified
scar hypertrophy by measuring the scar elevation index (SEI) on postoperative days 14, 21,
28, and 35 with ultrasonography. Wounds were harvested 35 days later for histomorphometric
and gene expression analysis.
RESULTS:
Intralesional injections of ADSCs or ADSCs-CM both led to scars with a far more normal
appearance and significantly decreased SEI (44.04 % and 32.48 %, respectively, both P
<0.01) in the rabbit ears compared with their internal controls. Furthermore, we confirmed
that collagen was organized more regularly and that there was a decreased expression of
alpha-smooth muscle actin (α-SMA) and collagen type Ι in the ADSC- and ADSCs-CM-
injected scars according to histomorphometric and real-time quantitative polymerase chain
reaction analysis. There was no difference between DMEM-injected and untreated scars.
CONCLUSIONS:
An intralesional injection of ADSCs reduces the formation of rabbit ear hypertrophic
scars by decreasing the α-SMA and collagen type Ι gene expression and ameliorating
collagen deposition and this may result in an effective and innovative anti-scarring
therapy.
Ref. 7
Int J Mol Sci. 2015 Aug 13;16(8):19027-39.
Human Dermal Stem/Progenitor Cell-Derived Conditioned Medium Improves
Senescent Human Dermal Fibroblasts.
Abstract
Adult skin stem cells are recognized as potential therapeutics to rejuvenate aged skin. We
previously demonstrated that human dermal stem/progenitor cells (hDSPCs) with multipotent
capacity could be enriched from human dermal fibroblasts using collagen type IV. However,
the effects of hDSPCs on cellular senescence remain to be elucidated. In the present study,
we investigated whether conditioned medium (CM) collected from hDSPC cultures (hDSPC-
CM) exhibits beneficial effects on senescent fibroblasts. We found that hDSPC-CM promoted
proliferation and decreased the expression level of senescence-associated β-galactosidase
in senescent fibroblasts. In addition, p53 phosphorylation and p21 expression were
significantly reduced in senescent fibroblasts treated with hDSPC-CM. hDSPC-CM restored
the expression levels of collagen type I, collagen type III, and tissue inhibitor of
metalloproteinase, and antagonized the increase of matrix metalloproteinase 1 expression.
Finally, we demonstrated that hDSPC-CM significantly reduced reactive oxygen species
levels by specifically up-regulating the expression level of superoxide dismutase 2. Taken
together, these data suggest that hDSPC-CM can be applied as a potential therapeutic
agent for improving human aged skin.

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Academic research of stem cell secretory factors in anti-aging skincare

  • 1. Academic articles of Stem Cell Conditioned Medium in Anti-aging Skin care www.silkah.com email: info@silkah.com
  • 2. Ref. 1 Source: Textbook of Aging skin, P. 209, Figure 20.10 Objective and subjective evaluation of the protein extracts from ADSC-CM in a large-scale (n= 235) pilot study in terms of: (a) winkles, (b) acquired pigmentary lesions, and (c) dilated pores. The evaluation score is based upon the following scales: 0= poor/ worsened; 1= no change; 2= fair/ mild improvement; 3= good/ moderate improvement; 4= excellent/ marked improvement. As compared to 47.4% showing good to excellent improvement in wrinkle (a), 63% of the patients were judged to have good to excellent improvement in acquired pigmentary lesions (b) and dilated pores (c).
  • 3. Ref. 2 Source: 2008.oct. Dermatol Surg; 34(10): P. 1323-6 Adipose-derived stem cells and their secretory factors as a promising therapy for skin aging. Adipose-derived stem cells (ADSCs) and their secretory factors can stimulate collagen synthesis and migration of fibroblasts during the wound healing process. Conventional treatments for skin aging, such as lasers and topical regimens, induce new collagen synthesis via activation of dermal fibroblasts or growth factors. Considering the results of our previous study, ADSCs can also be used for the treatment of skin aging. We demonstrated that ADSCs produce many useful growth factors, increase collagen production in animal study, and reverse skin aging in human trial. ADSCs and their secretory factors show promise for application in cosmetic dermatology, especially in the treatment of skin aging.
  • 4. Ref.3 2008.April, Biol Pharm Bull.; 31(4): P. 606-10 Whitening effect of adipose-derived stem cells: a critical role of TGF-beta 1. It has been demonstrated that adipose-derived stem cells (ADSCs) secrete cytokines and exhibit diverse pharmacological actions. The present study examined the unknown pharmacological action of ADSCs regarding whitening effects. ADSC-CM treatment inhibited the synthesis of melanin and the activity of tyrosinase in a dose dependent manner. Transforming growth factor-beta1 (TGF- beta 1), a potent regulator of melanogenic proteins, was neutralized by the addition of a blocking antibody to ADSC-CM, and down-regulated expression of tyrosinase and TRP1 was almost reversed. Collectively, these results indicate that secretary factors of ADSC inhibit melanin synthesis by down-regulating the expression of tyrosinase and TRP1, which are mainly mediated by TGF- beta1.
  • 5. Ref. 4 2008,April. PLoS One.; 3(4): P. e1886 Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. Bone marrow derived mesenchymal stem cells (BM-MSCs) have been shown to enhance wound healing; however, the mechanisms involved are barely understood. In this study, we examined paracrine factors released by BM-MSCs and their effects on the cells participating in wound healing compared to those released by dermal fibroblasts. BM-MSC-conditioned medium significantly enhanced migration of macrophages, keratinocytes and endothelial cells and proliferation of keratinocytes and endothelial cells compared to fibroblast-conditioned medium. Moreover, in a mouse model of excisional wound healing, where concentrated BM-MSC-conditioned medium was applied, accelerated wound healing occurred compared to administration of pre-conditioned or fibroblast- conditioned medium. Our results suggest that factors released by BM-MSCs recruit macrophages and endothelial lineage cells into the wound thus enhancing wound healing.
  • 6. Ref. 5 2009, Feb., J Dermatol Sci.期刊; 53(2): P. 96-102 Antiwrinkle effect of adipose-derived stem cell: activation of dermal fibroblast by secretory factors. Adipose-derived stem cells (ADSC) have wound-healing and antioxidant effects on human skin via secretion of growth factors and activation of dermal fibroblasts. Paracrine mechanism reducing ultraviolet-B (UVB)-induced wrinkles by ADSC is investigated in this study. To characterize the paracrine mechanism involving the antiwrinkle effect of ADSC, a conditioned medium of ADSC (ADSC-CM) was directly incubated in human dermal fibroblasts (HDF). UVB irradiation reduced the proliferation of HDF, but this was reversed by the pretreatment of ADSC-CM in a dose-dependent manner. In addition, the ADSC-CM increased the protein expression of collagen type I and decreased the protein level of matrix metalloproteinase 1 in HDF, which may account for the increased collagen contents in the dermis. Collectively, these results indicate that the ADSC and its secretory factors are effective for UVB-induced wrinkles, and the antiwrinkle effect is mainly mediated by reducing UVB-induced apoptosis and stimulating collagen synthesis of HDF.
  • 7. Ref. 6 Stem Cell Res Ther. 2015 Aug 18;6:145. Intralesional injection of adipose-derived stem cells reduces hypertrophic scarring in a rabbit ear model. Abstract INTRODUCTION: Redundant collagen deposition at sites of healing dermal wounds results in hypertrophic scars. Adipose-derived stem cells (ADSCs) exhibit promise in a variety of anti-fibrosis applications by attenuating collagen deposition. The objective of this study was to explore the influence of an intralesional injection of ADSCs on hypertrophic scar formation by using an established rabbit ear model. METHODS: Twelve New Zealand albino rabbits were equally divided into three groups, and six identical punch defects were made on each ear. On postoperative day 14 when all wounds were completely re-epithelialized, the first group received an intralesional injection of ADSCs on their right ears and Dulbecco's modified Eagle's medium (DMEM) on their left ears as an internal control. Rabbits in the second group were injected with conditioned medium of the ADSCs (ADSCs-CM) on their right ears and DMEM on their left ears as an internal control. Right ears of the third group remained untreated, and left ears received DMEM. We quantified scar hypertrophy by measuring the scar elevation index (SEI) on postoperative days 14, 21, 28, and 35 with ultrasonography. Wounds were harvested 35 days later for histomorphometric and gene expression analysis. RESULTS: Intralesional injections of ADSCs or ADSCs-CM both led to scars with a far more normal appearance and significantly decreased SEI (44.04 % and 32.48 %, respectively, both P <0.01) in the rabbit ears compared with their internal controls. Furthermore, we confirmed that collagen was organized more regularly and that there was a decreased expression of alpha-smooth muscle actin (α-SMA) and collagen type Ι in the ADSC- and ADSCs-CM- injected scars according to histomorphometric and real-time quantitative polymerase chain reaction analysis. There was no difference between DMEM-injected and untreated scars. CONCLUSIONS: An intralesional injection of ADSCs reduces the formation of rabbit ear hypertrophic scars by decreasing the α-SMA and collagen type Ι gene expression and ameliorating collagen deposition and this may result in an effective and innovative anti-scarring therapy.
  • 8.
  • 9. Ref. 7 Int J Mol Sci. 2015 Aug 13;16(8):19027-39. Human Dermal Stem/Progenitor Cell-Derived Conditioned Medium Improves Senescent Human Dermal Fibroblasts. Abstract Adult skin stem cells are recognized as potential therapeutics to rejuvenate aged skin. We previously demonstrated that human dermal stem/progenitor cells (hDSPCs) with multipotent capacity could be enriched from human dermal fibroblasts using collagen type IV. However, the effects of hDSPCs on cellular senescence remain to be elucidated. In the present study, we investigated whether conditioned medium (CM) collected from hDSPC cultures (hDSPC- CM) exhibits beneficial effects on senescent fibroblasts. We found that hDSPC-CM promoted proliferation and decreased the expression level of senescence-associated β-galactosidase in senescent fibroblasts. In addition, p53 phosphorylation and p21 expression were significantly reduced in senescent fibroblasts treated with hDSPC-CM. hDSPC-CM restored the expression levels of collagen type I, collagen type III, and tissue inhibitor of metalloproteinase, and antagonized the increase of matrix metalloproteinase 1 expression. Finally, we demonstrated that hDSPC-CM significantly reduced reactive oxygen species levels by specifically up-regulating the expression level of superoxide dismutase 2. Taken together, these data suggest that hDSPC-CM can be applied as a potential therapeutic agent for improving human aged skin.