Fig. 5. Engineering of a stem cell-based uterus.

a Co-culture systems to model the uterus during embryo implantation. Advances include vascularisation of endometrial organoids and integration of immune components. The co-culture of vascularised organoids alongside embryo should allow apposition assays if the polarity of organoids can be inverted. b Apposition, adhesion and trophoblast invasion could be modelled in complex tissue constructs engineered by layered deposition of 3D cell-embedded gels using 3D printing. c Automatised culture can be obtained by using organ-on-a-chip technology, allowing high-throughput screening of patient-derived uterine cells for co-culture and cell-invasion assays, but also enable linear stacking of multiple components of the female reproductive tract on-a-chip, such as ovarian and fallopian tube-cell containing chips. d Pathologies associated with the human uterus, such as a medically required surgical removal of the uterus or a lesion of the endometrial wall following cancer treatment, could be targeted with stem cell-based uteri. Patient-derived primary cells could be expanded in vitro, and seeded onto a de-cellularised donor uterus in order to avoid immune reaction of the patient following re-grafting of the donor uterus. Patient primary cell culture on a scaffold allows to obtain a cellularised grafting patch which can be transplanted to reconstitute the patient’s uterus.