Methods and compositions to generate a multicellular model of the human endometrium by differentiating pluripotent stem cells into endometrial stromal fibroblasts and co-culturing with placenta-derived endometrial epithelial organoids, with applications in drug discovery and screening.
Current treatments for endometrial and reproductive diseases are limited by inadequate models for human implantation and placentation. Most existing non-human animal models do not share fundamental biological processes with the human endometrium, such as spontaneous decidualization, and no existing human cell cultures recapitulate the cyclic interactions between endometrial stromal and epithelial compartments necessary for decidualization and implantation. Thus, mechanistic studies of processes involved in reproductive diseases and the evaluation of pre-clinical drug action and safety have traditionally been a challenge.
The invention addresses the limitations in drug development for reproductive conditions by providing a robust protocol to differentiate induced pluripotent stem cells into endometrial stromal fibroblasts. These cells are then co-cultured with endometrial epithelial organoids derived from term placenta, creating a multicellular model that mimics the human endometrial environment. The model is capable of responding to hormonal treatments and withdrawals, allowing for the comprehensive study of biological processes and drug effects throughout the endometrial cycle. Additionally, it can facilitate the examination of drug interactions with trophoblasts, offering a valuable tool for evaluating drug impacts during human pregnancy.
US Patent Pending