الفهرس 
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Abstract
Aging is a biological process that induces changes to the structural integrity and physiological function of skin resulting in the development of dyschromia, roughness, and fine wrinkles followed by persistent deeper folds. Structural changes are a result of dermal atrophy, decreased collagen, the loss of subcutaneous fat, the loss of inherent elasticity, and increased melanogenesis. Several theories have been proposed to explain this process, including the accumulation of genomic mutations, the accumulation of toxic metabolites, hormonal deprivation, the increased formation of free radicals (oxidative damage), and the cross-linking of macromolecules under glycation.
Stem cell-based therapy is becoming a promising new approach in almost every medical specialty. Over the past few years there has been tremendous scientific activity focused on this area of research (basic, preclinical as well as clinical), and rapidly growing evidence is accumulating to support the therapeutic potential of stem cells in skin tissue engineering and cutaneous wound healing. With stem cell administration, the medical practitioner would anticipate to achieve earlier wound closure, acceleration in healing, prevention of wound contracture and scar formation, and ideally regeneration of the skin and its appendages.
Stem cells reside in a specialized environment known as a niche that can control many aspects of stem cells’ behavior including proliferation, differentiation, and apoptosis. Mesenchymal stem cells (MSCs), also referred to as mesenchymal stromal cells, can be isolated from bone marrow and many other sources, such as adipose tissue, umbilical cord blood.
MSCs are the most promising and substantially evaluated stem cell type for their plasticity in tissue repair and regeneration. MSCs have the capability to differentiate into cells with the mesodermal, ectodermal and endodermal characteristics. They contribute to wound repair and regeneration through direct differentiation or transdifferentiation into tissue-specific cells to reconstitute the tissue. They also release paracrine factors to stimulate the survival and functional recovery of the resident cells. MSCs are found to have immune-regulatory potency in addition to their low immunogenicity feature. Their regulatory capacity enables the modulation of the local microenvironment or niche and the host immune response. As a result, enhanced angiogenesis and suppressed immune response are often observed after MSCs administration. MSCs also stimulate the proliferation of other progenitor cell populations within target organs to promote endogenous repair.
In terms of the anticipated clinical application, the use of non-fractionated, non-expanded stem cell sources is likely to be more attractive and offer significant advantages. Without subjecting the stem cells to additional extraction or culture expansion procedures, the application is more time-saving and contamination-avoiding. Moreover, using a heterogeneous population containing a rich source of various progenitor cells in addition to MSCs, and their associated growth factors, the application would have added values to the use of culture-expanded MSCs alone.
The aim of this study was to tackle the issue of skin aging utilizing autologous ASCs and BMSCs obtained from 10 recruits to be re-injected in specific sites that manifest signs of aging/photoaging. ASCs were delivered subcutaneously, within the unprocessed lipoaspirate (fat graft) that was obtained by tumescent liposuction and was re-injected in the right cheek and the dorsum of the right hand. BMSCs present within the mononuclear (buffy coat) constituent of the bone marrow aspirate that was obtained by density gradient centrifugation, were injected subcutaneously in the left cheek and the dorsum of the left hand in an attempt to evaluate the potential rejuvenative effect of these two types of MSCs.
Regarding clinical improvement in the hands, both ASCs and BMSCs achieved similar results concerning wrinkling and mottled hyperpigmentation, but BMSCs gave better results regarding solar lentigines. As for the face, the clinical improvement seen in both cheeks was very similar since the post treatment scores were quite close, rendering their comparison statistically non-significant.
A 3-mm punch biopsy was taken from the dorsi of both hands for histological evaluation of the changes brought upon by ASCs and BMSCs. The histological sections were stained by routine H&E, masson trichrome (for collagen fibers), aldehyde fuchsin (for elastic fibers) and fontana masson (for melanin).
Morphometric analysis of the histological findings was done using image analysis for assessment of the changes detected in collagen density, elastic fiber area percent as well as the staining intensity of melanin pigment. The results of the image analysis revealed an increase in collagen area percent, an increase the in elastic fiber area percent for both groups, and a decrease in the melanin area percent for the BMSCs-treated group. As for the melanin area percent in the ASCs-treated group, an increase was detected as compared to the pre-treatment values.
In addition, both groups resulted in a positive decorin expression by immunohistochemical staining post-treatment as compared to its negative expression in the pre-treatment specimens. Specimens of the ASCs-treated group demonstrated cut sections of sweat glands and their ducts aswell as an apparent increase in epidermal thickness, which was not observed in specimens of the BMSCs-treated group. These results suggest that ASCs have an added advantage over BMSCs concerning regeneration of the skin and its constituents.