Endometrial Perivascular Progenitor Cells and Uterus Regeneration

Abstract

Ovarian steroid-regulated cyclical regeneration of the endometrium is crucial for endometrial receptivity and embryo implantation, and it is dependent on the dynamic remodeling of the endometrial vasculature. Perivascular cells, including pericytes surrounding capillaries and microvessels and adventitial cells located in the outermost layer of large vessels, show properties of mesenchymal stem cells, and they are thus promising candidates for uterine regeneration. In this review, we discuss the structure and functions of the endometrial blood vasculature and their roles in endometrial regeneration, the main biomarkers and characteristics of perivascular cells in the endometrium, and stem cell-based angiogenetic therapy for Asherman's syndrome.

Keywords: Asherman’s syndrome; CD146 pericyte; CD34 adventitial cell; endometrial stem cell; perivascular cell.

Figure 1

The uterine vasculature. (a) Arterial blood supply of the ovaries, fallopian tubes, and uterus. (b) Radiographs of the transverse slice of the uterus in the mid-secretory phase, showing its arterial vasculature. Figure 1a is edited from the figure by Norris, C.C., Clark, J.G., and Peters, D. Gonorrhea in Women. 1913. Figure 1b is edited from the figure by Farrer-Brown, G., Beilby, J.O., and Tarbit, M.H. The Blood Supply of the Uterus. 1. Arterial Vasculature. J. Obstet. Gynaecol. Br. Commonw. 1970, 77, 673–681.

Figure 2

Perivascular cells in the human endometrium. (a) Co-staining of CD146 (green) and α-SMA (red) in human endometrial functionalis. G, glandular epithelial cell. (b) Cells expressing α-SMA in the tunica media are surrounded by CD34⁺ adventitial cells in human endometrial basalis. (c) Part of the CD34⁺ adventitial cells are co-stained with SUSD2. (d) CD34⁺ adventitial cells enclose CD146⁺ pericytes in large vessels in the human endometrium. V, vessel. (e) Schematic showing two groups of perivascular cells in the endometrium. Pericytes surrounding endothelial cells are located in microvessels in both functionalis and basalis, while adventitial cells reside in the outermost layer of large vessels, mainly in endometrial basalis. Figure 2a–d from Zhu, X., Yu, F., Yan, G., Hu, Y., Sun, H., and Ding, L. Human endometrial perivascular stem cells exhibit a limited potential to regenerate endometrium after xenotransplantation. Hum. Reprod. 2020.