RESUMEN
INTRODUCTION: Imedeen™ is a cosmeceutical that provides nutrients to the skin. One of its active ingredients is the Marine Complex™ (MC). AIM: The aim of this study was to evaluate whether MC affects skin morphogenesis differently in female and male human skin equivalents (HSEs). METHODS: Human skin equivalents were established with cells obtained from female or male donors between 30 and 45 years of age and cultured for seven or 11 weeks in the presence or absence of MC. Using immunohistochemistry, we examined early differentiation by keratin 10 expression, (hyper)proliferation by keratin 17 and Ki67, and basement membrane composition by laminin 332 and collagen type VII. In addition, the expression of collagen type I and the secretion of pro-collagen I were measured. RESULTS: Marine Complex strongly increased the number of Ki67-positive epidermal cells in female HSEs. In the dermis, MC significantly stimulated the amount of secreted pro-collagen I and increased the deposition of laminin 332 and collagen type VII. Furthermore, MC prolonged the viable phase of HSEs by slowing down its natural degradation. After 11 weeks of culturing, the MC-treated HSEs showed higher numbers of viable epidermal cell layers and a thicker dermal extracellular matrix compared with controls. In contrast, these effects were less pronounced in male HSEs. CONCLUSION: The MC nutrient positively stimulated overall HSE tissue formation and prolonged the longevity of both female and male HSEs. The ability of MC to stimulate the deposition of basement membrane and dermal components can be used to combat 2 human skin aging in vivo.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Dermis/citología , Células Epidérmicas , Extractos de Tejidos/farmacología , Supervivencia Tisular/efectos de los fármacos , Adulto , Membrana Basal/efectos de los fármacos , Membrana Basal/metabolismo , Moléculas de Adhesión Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Colágeno Tipo I/metabolismo , Colágeno Tipo VII/metabolismo , Dermis/metabolismo , Epidermis/metabolismo , Femenino , Fibroblastos , Humanos , Queratina-10/metabolismo , Queratina-17/metabolismo , Queratinocitos , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Fenómenos Fisiológicos de la Piel/efectos de los fármacos , KalininaRESUMEN
IL-7 is a central cytokine in the development of hematopoietic cells, although interspecies discrepancies have been reported. By coculturing human postnatal thymus hematopoietic progenitors and OP9-huDL1 stromal cells, we found that murine IL-7 is approximately 100-fold less potent than human IL-7 for supporting human T cell development in vitro. We investigated the role of human IL-7 in newborn BALB/c Rag2(-/-)gamma(c)(-/-) mice transplanted with human hematopoietic stem cells (HSC) as an in vivo model of human hematopoiesis using three approaches to improve IL-7 signaling: administration of human IL-7, ectopic expression of human IL-7 by the transplanted human HSC, or enforced expression of a murine/human chimeric IL-7 receptor binding murine IL-7. We show that premature IL-7 signaling at the HSC stage, before entrance in the thymus, impeded T cell development, whereas increased intrathymic IL-7 signaling significantly enhanced the maintenance of immature thymocytes. Increased thymopoiesis was also observed when we transplanted BCL-2- or BCL-x(L)-transduced human HSC. Homeostasis of peripheral mature T cells in this humanized mouse model was not improved by any of these strategies. Overall, our results provide evidence for an important role of IL-7 in human T cell development in vivo and highlight the notion that IL-7 availability is but one of many signals that condition peripheral T cell homeostasis.