Photoaged Skin Therapy with Adipose-Derived Stem Cells

Background: The major intrinsic cause of facial skin degeneration is age, associated with extrinsic factors such as exposure to sun. Its major pathologic causes are degeneration of the elastin matrix, with loss of oxytalan and elaunin fibers in the subepidermal region, and actinic degeneration of elastin fibers that lose their functional properties in the deep dermis. Therapy using autologous adipose mesenchymal stem cells for regeneration of extracellular matrix in patients with solar elastosis was addressed in qualitative and quantitative analyses of the dermal elastic fiber system and the associated cells. Methods: Mesenchymal stem cells were obtained from lipoaspirates, expanded in vitro, and introduced into the facial skin of patients submitted after 3 to 4 months to a face-lift operation. In the retrieved skin, immunocytochemical analyses quantified elastic matrix components; cathepsin K; matrix metalloproteinase 12 (macrophage metalloelastase); and the macrophage M2 markers CD68, CD206, and hemeoxygenase-1. Results: A full de novo formation of oxytalan and elaunin fibers was observed in the subepidermal region, with reconstitution of the papillary structure of the dermal-epidermal junction. Elastotic deposits in the deep dermis were substituted by a normal elastin fiber network. The coordinated removal of the pathologic deposits and their substitution by the normal ones was concomitant with activation of cathepsin K and matrix metalloproteinase 12, and with expansion of the M2 macrophage infiltration. Conclusion: The full regeneration of solar elastosis was obtained by injection of in vitro expanded autologous adipose mesenchymal stem cells, which are appropriate, competent, and sufficient to elicit the full structural regeneration of the sun-aged skin.