From the Programa de Pós-Graduação em Ciências Cirúrgicas and the Instituto de Biofísica Carlos Chagas Filho, Laboratório de Imunopatologia, Universidade Federal do Rio de Janeiro; the Dipartamento di Scienze Neurologiche e del Movimento, Sezione di Anatomia e Istologia della Universitá degli Studi di Verona; the Unità di Chirurgia Rigenerativa dela Clinica San Francesco; and the Centro de Medicina Regenerativa, Faculdade de Medicina de Petrópolis.
Plast Reconstr Surg. 2020 Jun;145(6):1037e-1049e. doi: 10.1097/PRS.0000000000006867.
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.
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.
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.
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.
CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
面部皮肤退化的主要内在原因是年龄，与暴露于太阳等外在因素有关。其主要病理原因是弹性蛋白基质的退化，导致皮下区域的 oxytalan 和 elaunin 纤维丧失，以及真皮深层光化弹性纤维的变性，使其丧失功能特性。在定性和定量分析真皮弹性纤维系统及其相关细胞的基础上，探讨了利用自体脂肪间充质干细胞治疗光化弹性纤维病患者细胞外基质再生的问题。
从脂肪抽吸物中获取间充质干细胞，在体外扩增，并在 3 至 4 个月后面部提升手术后将其引入患者的面部皮肤。在取出的皮肤中，免疫细胞化学分析定量了弹性基质成分；组织蛋白酶 K；基质金属蛋白酶 12（巨噬细胞金属弹性蛋白酶）；以及巨噬细胞 M2 标志物 CD68、CD206 和血红素加氧酶-1。
在皮下区域观察到 oxytalan 和 elaunin 纤维的全新形成，真皮-表皮交界处的乳头结构得到重建。真皮深层的弹性纤维沉积被正常的弹性纤维网络所取代。病理性沉积物的协调清除及其被正常沉积物取代与组织蛋白酶 K 和基质金属蛋白酶 12 的激活以及 M2 巨噬细胞浸润的扩张同时发生。
通过注射体外扩增的自体脂肪间充质干细胞，可获得光化弹性纤维病的完全再生，这些细胞适合、有能力且足以引发阳光老化皮肤的完全结构再生。
临床问题/证据水平：治疗，IV 级。
