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Orgun et al. Regenerative mechanisms of adipose-derived stem cells

and hypoxia inducible factor-1a (HIF-1a) by the ASCs and keratinocytes led to epithelialization of full
preconditioned ASCs. [35] thickness wounds with minimal wound contracture.
The authors claimed that this improvement in wound
There have been several clinical studies conducted healing was due to the paracrine secretions of ASCs.
on human patients as well. Lee et al. [36] investigated Moreover, co-administration of acellular conditioned
the clinical safety of ASCs administration in patients medium (CM) from ASCs cultures with PRP increased
with critical limb ischemia. Two thirds of the patients keratinocyte and fibroblast proliferation, [42] as well as
showed significant clinical improvement by complete keratinocyte maturation. [43]
wound healing and formation of collateral vessels
in the affected area. There were no side effects or There is also evidence that ASCs could differentiate
undesirable outcomes after treatment. The authors into keratinocyte-like cells and express keratinocyte
suggested that the improvement was due to the specific markers when co-cultured on a fibroblast
angiogenic paracrine properties of ASCs; however, layer. [44,45]
the lack of histological and molecular evaluation of the
results deems it impossible to offer a clear scientific Zografou et al. [46,47] have investigated the effects of
explanation. Even though the beneficial effects of transplanted autologous ASCs on full thickness skin
ASCs such as their differentiation capacity and graft survival and wound healing in diabetic rats.
secretion of pro-angiogenic factors are confirmed in Graft survival was improved compared with control.
vitro, the exact mechanisms for their in vivo activity are Curiously, ASCs showed arrangement in tubular
not well established. More clinical studies are needed structures which were positively stained with both
to fully comprehend the therapeutic abilities of ASCs VEGF and von Willebrand Factor (vWF) staining in
in wound healing in order to construct standardized vivo. Increased tissue expression of TGF-β3 and
treatment modalities in the future. VEGF were shown in skin grafts with transplanted
ASCs by the same group in another study.
THE EFFECTS OF ASCs ON WOUND
HEALING There is also evidence that ASCs have lifesaving effects
on the residing cells of tissues after an ischemic insult.
Chronic wounds are a prominent health issue all A study by Hao et al. [48] showed that transplantation
around the world and the management of these of ASCs inhibited myocyte apoptosis in the ischemic
wounds is challenging. Diabetic ulcers, venous ulcers muscle.
and pressure ulcers represent 80-90% of all chronic
wounds. [37] Even with optimal conditions, the healing Unfortunately, topical or injected ASCs usually tend
process mostly leads to scarring and fibrosis. Many to stay in the applied location and fail to effectively
cases fail to heal and lead to amputations of the lower migrate. The delivery method of ASCs to wounds
extremity, which are very debilitating for the patient. has been a thoroughly investigated topic of great
In addition, these wounds usually have superposed importance. Delivery systems which supply a
infection, and if not treated correctly may lead to sepsis favorable microenvironment for the ASCs to survive
or even death. [38] The importance and high prevalence are suggested to increase their regenerative effects.
of chronic wounds provoked numerous investigations For example, administration of ASCs to open wounds
in order to find a better treatment for these wounds. The on a silk fibroin-chitosan scaffold accelerated wound
positive effects of ASCs on wound healing inchronic closure and new vessel formation. ASCs delivered by
and complex wounds (such as anorectal fistula due to the scaffold infiltrated into the proliferating epithelium
Crohn disease) have been well demonstrated. [39] It is and vascular tissue and expressed smooth muscle
critical to consider that the animal wound models used actin, also differentiated into cells similar to of the
in these studies are different than human wounds in epidermal epithelium. [40] Currently, scaffolds are also
many aspects; however, the results are promising. being used to induce differentiation of ASCs into
specific cell lines. [49]
There is evidence that ASCs could be contributing
to the healing of both mesodermal (i.e. dermis) and There is an increase of radiation injuries and
ectodermal (i.e. keratinocytes) derived tissues in wounds with the widespread use of radiotherapy,
the wound. [40] The interaction between ASCs and interventional radiological or cardiological procedures,
keratinocytes has been a subject of interest and a and radioactive material intake for nuclear medicine
fair amount of investigation has been done regarding related scans or treatments. Chronic radiation wounds
this issue. Ozpur et al. [41] has demonstrated that the usually cannot be treated with conventional methods
administration of a fibrin matrix seeded with both such as flap surgery or skin grafting because of
36 Plastic and Aesthetic Research ¦ Volume 4 ¦ March 22, 2017