Human Endometrial Reconstitution From Somatic Stem Cells: The Importance of Niche-Like Cells

Endometrial regeneration has long been proposed to be mediated by stem cells, but the isolation of endometrial stem cells has been hampered by a lack of validated markers. Specific markers would enable isolation of these stem cells, thereby promoting advancements in regenerative medicine for the treatment of endometrial diseases and dysfunctions. We sought to investigate the regenerative ability of human endometrial positive for sushi domain containing 2/intercellular adhesion molecule 1 (SUSD2⁺/ICAM1⁺) cells and Side Population cell lines in a xenograft mice model. The injection of total endometrial cell suspensions and Side Population cell lines under kidney capsules induced neoformation of human endometrium verified by the presence of typical endometrial markers (vimentin, cytokeratin 18, and progesterone receptor) by immunofluorescence. Total endometrial cell types promoted a better reconstitution in comparison to injecting ICAM1⁺ and SUSD2⁺ cells alone. The endometrial fraction is probably acting as a niche, resulting in increased reconstruction efficiency of pure fractions. Human engrafted cells were localized near blood vessels and induced the proliferation of surrounding cells. Our results suggest that human endometrial Side Population, a heterogeneous population possibly harboring endometrial stem cells, has the optimum capacity to regenerate endometrial-like tissue. In contrast, cells positive for single stem cell markers SUSD2 and ICAM1 have minimally functional regenerative capacities in the absence of niche-like cells.