Building a stem cell-based primate uterus

Abstract

The uterus is the organ for embryo implantation and fetal development. Most current models of the uterus are centred around capturing its function during later stages of pregnancy to increase the survival in pre-term births. However, in vitro models focusing on the uterine tissue itself would allow modelling of pathologies including endometriosis and uterine cancers, and open new avenues to investigate embryo implantation and human development. Motivated by these key questions, we discuss how stem cell-based uteri may be engineered from constituent cell parts, either as advanced self-organising cultures, or by controlled assembly through microfluidic and print-based technologies.

Endometrial organoids derived from Mayer–Rokitansky–Küster–Hauser syndrome patients provide insights into disease-causing pathways

“…The two latter methods come with a plethora of ethical difficulties, and researchers and clinicians are working urgently to find new ways of providing larger groups of patients with a cure. Organ-on-a-chip-based methods as well as using animals or deceased patient uterus scaffolds represent opportunities for uteri reconstruction using patient-specific cells to overcome limitations of transplantation approaches ( Bergmann et al, 2021 ). The development of these techniques in combination with an in-depth understanding of uterine development might mark a milestone for achieving a long-term treatment solution to some of the most severe uterine pathologies such as MRKH syndrome.…”

“…Our study shows that MRKH endometrial organoids are hormone responsive and show a high similarity to healthy endometrial epithelial cells. Future research in this emerging line of research, however, should reveal whether this is sufficient for successful embryo implantation in a to-be-developed de novo uterus from MRKH patient cells ( Alzamil et al, 2021 ; Bergmann et al, 2021 ).…”

Microfluidics for Neuronal Cell and Circuit Engineering

“…In conclusion, microfluidics-based 3D neuronal circuit engineering techniques are flexible and support the culture of brain organoids and the development of brain-on-a-chip models. ,, Unlike brain-on-a-chip models, brain organoids faithfully replicate fetal neocortex development while also exhibiting segregated brain regions, cell type heterogeneity, and brain-endogenous gene expression programs. , On the other hand, while brain organoid platforms often fail to provide tools for controlling the cellular microenvironment, brain-on-a-chip models are compatible with microenvironmental control as they incorporate diverse microfluidic concepts. , Low throughput and lack of reproducibility, however, remain as major challenges in the organoid field . Initial attempts at adapting droplet-based microfluidic concepts, which have been exploited extensively for single-cell sorting and sequencing, are being undertaken as to generate uniform organoids at scale .…”

“…Initial attempts at adapting droplet-based microfluidic concepts, which have been exploited extensively for single-cell sorting and sequencing, are being undertaken as to generate uniform organoids at scale . Such a robust platform could enhance the translational capacity of human-derived brain organoids and upgrade their physiological relevance. , In turn, brain region-specific organoids − can also be adapted to multicompartment microfluidic devices to engineer on-chip assembloids. Similar to two-layered 2D and 3D network structures in compartmentalized microfluidic devices, 3D brain region-specific organoids could also be studied in physically and chemically isolated environments while synaptically interacting with each other.…”

“…458,459 In conclusion, microfluidics-based 3D neuronal circuit engineering techniques are flexible and support the culture of brain organoids and the development of brain-on-a-chip models. 447,460,461 Unlike brain-on-a-chip models, brain organoids faithfully replicate fetal neocortex development while also exhibiting segregated brain regions, cell type heterogeneity, and brain-endogenous gene expression programs. 34,131 On the other hand, while brain organoid platforms often fail to provide tools for controlling the cellular microenvironment, brain-on-a-chip models are compatible with microenvironmental control as they incorporate diverse microfluidic concepts.…”