Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium

TLDR

Human endometrium regenerates ~5 mm per week, and a small colony‑forming stromal cell population has been proposed as mesenchymal stem cells. The study aimed to test whether CD146+PDGF‑Rβ+ cells can be prospectively isolated as MSC‑like endometrial stromal cells and to map their location. Researchers sorted endometrial stromal cells by FACS into CD146+PDGF‑Rβ+ and CD146−PDGF‑Rβ− groups, then assessed colony formation, multilineage differentiation, MSC marker expression, and performed immunostaining of tissue sections. CD146+PDGF‑Rβ+ cells, comprising ~1.5 % of the stromal population, were enriched for colony‑forming ability (7.7 % vs 0.7 %) and differentiated into adipogenic, osteogenic, myogenic, and chondrogenic lineages, expressed MSC surface markers, and were perivascular; thus, a small MSC‑like population likely underlies endometrial regeneration and offers a readily available source for tissue engineering.

Abstract

Human endometrium has immense regenerative capacity, growing ~5 mm in 7 days every month. We have previously identified a small population of colony-forming endometrial stromal cells which we hypothesize are mesenchymal stem cells (MSC). The aim of this study was to determine if the co-expression of two perivascular cell markers, CD146 and platelet-derived growth factor-receptor β (PDGF-Rβ), will prospectively isolate endometrial stromal cells which exhibit MSC properties, and determine their location in human endometrium. Single cell suspensions of human endometrial stromal cells were fluorescence activated cell sorting (FACS) sorted into CD146+PDGF-Rβ+ and CD146−PDGF-Rβ− populations and analysed for colony-forming ability, in vitro differentiation and expression of typical MSC markers. Full thickness human endometrial sections were co-stained for CD146 and PDGF-Rβ. FACS stromal CD146+PDGF-Rβ+ stromal cells (1.5% of sorted population) were enriched for colony-forming cells compared with CD146−PDGF-Rβ− cells (7.7 ± 1.7 versus 0.7 ± 0.2% P <0.0001), and also underwent differentiation into adipogenic, osteogenic, myogenic and chondrogenic lineages. They expressed MSC phenotypic surface markers and were located near blood vessels. This study shows that human endometrium contains a small population of MSC-like cells that may be responsible for its cyclical growth, and may provide a readily available source of MSC for tissue engineering applications.