![]() ![]() Three-dimensional models used to recreate the endometrium in vitro incorporate ECM-derived matrices such as collagen I and basement membrane extract ( Schutte and Taylor, 2012 Asmani et al., 2013 Bayat et al., 2016 Fayazi et al., 2017). The human endometrium consists of an epithelial and a stromal compartment supported by an endogenous niche of stem cells, a vascular compartment, and a population of immune-resident cells ( Carrascosa et al., 2018). ![]() To achieve successful implantation and placentation, the endometrial ECM is drastically modified along with changes to the luminal epithelium ( Guillemot, 1999 Kaloglu and Onarlioglu, 2010 Carrascosa et al., 2018). The ECM has a unique composition in each tissue including the endometrium, the mucous layer lining the lumen of the uterus and undergoing scar-free remodeling during the menstrual cycle. Disruption of ECM homeostasis can lead to fibrotic diseases, such as systemic sclerosis, liver cirrhosis, and cardiovascular disease, and can facilitate tumor malignancy and metastatic progression in cancer ( Cox and Erler, 2011). It also provides biochemical cues for tissue homeostasis, angiogenesis, immune response, and tissue repair ( Frantz et al., 2010 Rozario and DeSimone, 2010 Evangelatov and Pankov, 2013 Theocharis et al., 2016 Saldin et al., 2017). The extracellular matrix (ECM) is a complex mixture of fibrous proteins and acts as a physical substrate for cell adhesion, structure, and mechanical stimulation. Biomimetic endometrial milieus offer new strategies in reproductive techniques and endometrial repair and our findings demonstrate that EndoECM has potential for in vitro endometrial culture and as treatment for endometrial pathologies. Finally, EndoECM was injected subcutaneously in immunocompetent mice in a preliminary study to test a possible hypoimmunogenic reaction. Endometrial co-cultures remained viable and showed significant remodeling. Further, we developed a three-dimensional endometrium-like co-culture system of epithelial and stromal cells from different origins. EndoECM supported in vitro culture of human endometrial cells in two- and three-dimensional conditions and improved proliferation of endometrial stem cells with respect to collagen and Matrigel. The matrisome showed conservation of structural and tissue-specific components with low amounts of immunoreactive molecules. ![]() After decellularization and detergent removal, we investigated the physicochemical features of the EndoECM, including gelation kinetics, ultrastructure, and proteomic profile. We obtained endometrium derived from porcine decellularized uteri to create endometrial extracellular matrix (EndoECM) hydrogels.
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