De- and recellularization of the pig uterus: a bioengineering pilot study.

Absolute uterine factor infertility, or the absence of a functional uterus, has a prevalence of 3%-5% in the general population. Despite the great strides being made in reproductive medicine, patients diagnosed with absolute uterine factor infertility remain untreatable. The only available solution has been gestational surrogacy, but recently the Brannström group presented a viable alternative by reporting the first successful live birth after uterus transplantation. Similar to other transplantations, this approach has inherent limitations such as the paucity of donor organs and the need for long-term immunosuppression. Whole organ de- and recellularization, a novel tissue engineering approach within the field of regenerative medicine, could eventually provide another solution. Several groups have described animal models in which they have performed decellularization of whole uteri, while maintaining the extracellular matrix to enable recellularization attempts. Our work offers a new perspective; in decellularizing the porcine uterus, this constitutes the first pilot study using large whole reproductive organs. We demonstrated the preservation of a reusable/functional extracellular matrix while maintaining its vascular network. Furthermore, we report the first use of human side population stem cells in the successful recellularization of small acellular disk scaffolds procured from the decellularized organs. To conclude, this research opens new avenues in whole uterus bioengineering, opening the way towards the transplantation of functional bioengineered uteri into humans.

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.