Adipose-Derived Stem Cells and their Application in Stem Cell Creams
Borna Sarker and Vedanti Upadhyaya
Microanatomy, Dr. Robert Blystone
Trinity University Biology Department, San Antonio, TX
ABSTRACT
REVIEW OF PUBLICATIONS
CONCLUSION
Adipose-derived stem cells have been found to confer many
advantages in stem cell therapies and potential anti-aging
treatments, including stem cell creams and topical
medications. Our objective is to present and review findings
from the relevant literature in the field that pertain to the
benefits of adipose-derived stem cells and the mechanisms
that underlie their potential as components in topical
medications targeted at reducing the effects of extrinsic
aging due to overexposure to UV radiation.
Based on our reviews of findings in the literature, we
conclude that adipose-derived stem cells result in an antiaging effect through their paracrine function. Also, they may
have favorable effects on photo-aged fibroblasts at both the
cell cycle and genetic levels as demonstrated through
studies of p16 gene expression and metallopeptidase
function. Thus far it is suggested that the mechanism by
which wrinkle reduction occurs in photo-damaged skin
involves the following steps: fibroblasts produce collagen,
adipose-derived stem cells secrete cytokines that are
involved in collagen synthesis; an increase in collagen
density in the dermis occurs, which leads to dermal
thickness and a subsequent reduction in wrinkles. Further
studies should focus on translating this knowledge to stem
cell creams or other products, with the hope of creating
topical medications that have anti-aging properties derived
from the use of adipose-derived stem cells.
INTRODUCTION
REFERENCES
Cosmetics companies are now turning to biological
and chemical research to develop more advanced beauty
products. Specifically, the utilization of stem cell therapies
to help regenerate tissues of the aging skin is increasingly
being viewed as a potentially effective anti-aging treatment
by companies that make beauty products. As a result, much
effort has been put into understanding the processes behind
the aging of the skin.
Overexposure to UV radiation facilitates photo-aging,
a subtype of extrinsic aging, which is characterized by fine
and coarse wrinkles, dryness, and roughness in texture of
the epidermis. In addition, extrinsic aging leads to
decreased epidermal thickness and abnormal functioning of
keratinocytes. Another important characteristic of aged skin
is the fragmentation of the collagen matrix in the dermis;
this occurs because of metalloproteinases and UV-induced
up-regulation of collagenase gene expression. Therefore,
one focus of treatments is to reduce collagen collapse and
to stimulate its renewal through the use of stem cells.
Stem cells have various favorable potential uses that
are achieved through differentiation and paracrine
effects in most medical fields. Specifically, since there are
ample amounts of adult stem cells in the human body and
since they are easily accessible for harvest and clinical use,
they do not pose the same ethical problems as those posed
by the use of embryonic stem cells in therapy. Additionally,
the possibilities of an immunologic reactions are less likely
because the cells originate from autologous stem cells.
Mesenchymal stem cells, a type of undifferentiated
adult stem cell, are present as differentiated cells in tissues
or organs including subcutaneous fat, muscle and cartilage.
Furthermore, mesenchymal stem cells have the possibility of
self-renewal and differentiation into various tissues such as
adipocytes, osteocytes, and chondrocytes.
RESEARCH POSTER PRESENTATION DESIGN © 2012
www.PosterPresentations.com
From recent studies pertaining to the investigation of dermatological applications of stem cell therapies, adipose-derived stem
cells (ADSC) are known to be able to restore injured tissue via differentiation and paracrine effects (Song et al. 2011). In their
study, Seung Yong Song and his research team focused on investigating the effects of ADSC on photo-aged human dermal
fibroblasts (HDF), which play an important role in skin integrity and maintenance, based on paracrine function. In particular, they
strove to determine a more effective method of ADSC application and observe the fate of the photo-aged fibroblasts.
Jae-Hong Kim and colleagues conducted studies that indicated wrinkles are reduced by increasing dermal thickness and collagen
density after ADSC injection into photo-damaged aged skin. Histopathology showed that the number of fibroblasts and collagen
density increased in the ADSC-injected skin compared to the skin without injected ADSC. Their results suggested that this
increase in collagen density in the dermis was mainly mediated by increased collagen production by dermal fibroblasts. On
Western blot, which was carried out to evaluate the expression of type I procollagen and a protein that encodes for collagenase
called matrix metallopeptidase 13 (MMP-13), the expression of type I procollagen was significantly increased in the ADSC-injected
skin compared with the cell media–injected control. ADSC injection increased collagen synthesis but not collagenase in the dermis
(Kim, J. et al. 2011).
Moreover, there have been reports that collagen synthesis mediated by fibroblast activation plays an important role in skin
rejuvenation. ADSC secretes variable cytokines that modulate extracellular matrix remodeling, angiogenesis, antioxidant effect. In
this process, variable cytokines such as interleukin one (IL-1), tumor necrosis factor-alpha (TNF-α), transforming growth factorbeta (TGF-β), insulin-like growth factor (IGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF),
platelet derived growth factor (PDGF), and other growth factors participate in collagen synthesis. At first, these factors are
released from platelets, and then variable cytokines and growth factors are secreted from inflammatory cells and fibroblasts,
which act as the target tissue. This result indirectly suggests that the positive role of ADSC transplantation in aging skin may be
related to its paracrine activities to excrete angiogenic, anti-apoptotic and mitogenic factors for skin fibroblast rather than its
self-renewal and proliferative function (Kim, W.S. et al. 2009).
Furthermore, an age-dependent increase of expression of the p16 tumor-suppressor gene has been reported. When p16, which
controls the cell cycle and is also a cell senescence marker, is expressed, cells are arrested in the G1 phase, cell proliferation
stops, and senescence occurs. In addition, after UV irradiation, p16 expression was found to decrease significantly in the HDFs
injected with ADSCs compared to those that were not injected with ADSCs. This result suggests that ADSC can reverse damage in
photo-aged fibroblasts. The effect of ADSC may not be a simple restoration of photo-damaged fibroblasts but a reverse of the
aging process at a genetic level (Song et al. 2011). However, further studies using other senescence markers need to be done to
further investigate this phenomenon.
Kim, J., et al. (2011) Adipose–derived stem cells as a new
therapeutic modality for ageing skin. Experimental
Dermatology 20, 383-387.
Kim, W.-S., et al. (2009) Antiwrinkle effect of adiposederived stem cell: Activation of dermal fibroblast by
secretory factors. Journal of Dermatological Science 53, 96102.
Kim, W.-S., et al. (2009) The wound-healing and antioxidant
effects of adipose-derived stem cells. Expert Opin. Biol.
Ther. 9, 879-887.
Rinaldi, A. (2008) Healing Beauty? EMBO Reports 9, 10731077.
Song, S., et al. (2011) Determination of adipose-derived
stem cell application on photo-aged fibroblasts, based on
paracrine function. Cytotherapy 13, 378–384.
ACKNOWLEDGEMENTS
We sincerely thank Dr. Robert Blystone for his guidance.