Development of a re-engineered cell-derived matrix for a skin aging model in tissue level

Abstract

There have been a number of aging models in multiscale level to investigate the effects of aging on human beings over the past decades. However, most aging models were for research at the cellular level, the organ level, or the system level, aging models at the tissue level, particularly in vitro models, are still lacking to date. Therefore, we propose here an in vitro skin aging model, as skin is the representative organ which shows the most prominent changes in aging, using a re-engineered fibroblast-derived extracellular matrix (FDM) optimized for the aging research at the tissue level. Today, diverse theories about aging have been studied, and among them, the glycation has recently received exceptional attention as an important mechanism of aging. Based on this, we stimulated the formation of the advanced end glycation products (AGEs) via glycation and UV irradiation to induce structural changes and loss of mechanical integrity within the matrix, thereby mimicking intrinsic and extrinsic aged skin, respectively. Through reseeding fibroblasts on each matrix, we observed their reduced proliferation and survival, quantitatively analyzed the morphological features, and furthermore identified the influence of the changes with aging at the matrix level on the cellular level. We developed more physiologically relevant in vitro skin aging model, and conclusively our in vitro model system would provide a potential platform for studying anti-AGE strategies that may be beneficial on skin aging.