Serious injuries of the endometrium (the innermost lining layer of the uterus) or naturally thin endometrium can cause uterine dysfunction and subsequently predispose patients to infertility or miscarriage. In this context, many stem cell researchers have devoted effort to the regeneration of injured or thin endometrium by administering various types of stem cells. Despite some promising initial results, regenerating the endometrium with stem cells is very challenging, as the lack of a 3D microenvironment for the transplanted stem cells leads to weak therapeutic effects. Therefore, as an alternative, we developed a novel endometrial stem cell-laden 3D artificial endometrium by combining various endometrial cellular components and natural biodegradable polymers to mimic the multilayered endometrial structure and its microenvironment. The artificial endometrium constitutes a triple-layered structure that recapitulates the structural and physiological features of the human endometrium. The cell viability and biological characteristics of various types of encapsulated endometrial cells are well maintained within the artificial endometrium, which exhibits similar behavior to the human endometrium by properly responding to steroid hormones and actively secreting various growth factors. Remarkably, severe degenerative changes were significantly relieved by artificial endometrium transplantation. More importantly, successful pregnancy and subsequent successful live birth without any phenotypic or genetic abnormalities can be achieved by transplanting our artificial endometrium into endometrial ablation mice.
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