Stem Cell Therapy to Approach Refractory Asherman’s Syndrome

Abstract

The endometrium is a highly regenerative tissue that regenerates every month after each menstrual cycle. Its main function is to enable implantation of the embryo at the right moment. If implantation of the embryo does not occur, the endometrium is partially destroyed and menstruation takes place, producing a new generation of tissue (upper 2/3) in the next menstrual cycle. This endometrial renewal (‘self-renewal’) is mostly regulated by hormones during 400–500 cycles during a woman’s reproductive lifetime. Only tissues with high cellular turnover, such as epidermis, gut epithelium, and bone marrow, have this high cellular turnover. An increasing amount of evidence supports that this process is regulated by endometrium-derived stem cells (EDSCs) [1]. Histologically, the endometrium is divided in two functional layers: the basal and functional layers. The functional layer responds to progesterone and estradiol, and this layer is completely shed during menstruation. The basal layer does not respond to hormones and also does not suffer desquamation, from which it regenerates the mucosa. Recent studies [2] have described the transcriptomic signature of the endometrium at a single cell level, showing that the endometrium is composed of six major cell types including ciliated and non-ciliated epithelia, stromal cells, endothelial cells, lymphocytes, and macrophages. Interestingly, in this study, four major phases of endometrial transformation are described and provide evidence for direct interplay between stromal fibroblasts and lymphocytes during decidualization, and an abrupt transcriptomic opening of the window of implantation takes place at mid-secretory phase in unciliated epithelial cells.