# Integrating tissue engineering and microfluidics to model the spatial niches of the human endometrium in vitro with guidance from in vivo multiomics data

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2024 · $573,160

## Abstract

The endometrium -- the innermost mucosal lining of the uterus that provides the site of embryo
implantation- is crucial for our species preservation and alterations on its function underlay infertility and
disease. Developments in single-cell and spatial technologies have illuminated previously unknown subtypes
of cells and their spatial arrangements in the endometrium, providing valuable insights into the signalling
pathways involved in the different endometrial compartments and hinting at their roles in determining cell
specification in the luminal or basal zones. While inferences can be made from these static pictures about
physiological functions ranging from blastocyst implantation and invasion to heavy menstrual bleeding, without
tractable in vitro models that capture the endometrium's dynamic spatial interactions, mechanistic hypotheses
about endometrial function remain challenging to test. Here, we develop in vitro models of the endometrium
by combining tissue-level spatial mapping approaches with in vitro tissue engineering and microfluidic
approaches. We will refine existing approaches and develop/test new models, prioritizing robustness and
reproducibility, and allowing dissemination and implementation by the broader community, as follows
Aim 1: Design a robust and scalable microphysiological systems (MPS) model that replicates the spatial
niches of the human endometrium in the early-to-mid secretory phase. We we will use a co-culture of epithelia
and stroma in a microfluidic device, in which organoids undergo morphogenesis in a special hydrogel. We will
inform the media composition and other metrics by querying the in vivo cellular atlases.
Aim 2: Quantify the interplay between cell origin (“nature”) and spatial environment (“nurture”) in defining
epithelial cell identity in the in vitro models built in Aim 1. We will use single-cell and spatial transcriptomics
technologies to profile the devices, and we will use clonal tracing to map the origin of a cell type. By integrating
vivo/in vitro datasets, we will conduct a systematic investigation into the various parameters that characterize
the cell source (such as luminal / basalis), as well as the magnitudes of gradients in diffusible signaling
molecules and nutrients.
Aim 3: Investigate the functional consequences of introducing endothelial cells into the in vitro model from
Aim 1, using a simple “monolayer” protocol. We will focus on the cell state transitions that are modulated by
endothelial-stromal-epithelial crosstalk during decidualization, and use the model to investigate immune cell
trafficking. Our ultimate goal is to obtain a systems biology view of the tissue, which will allow us to inform the
development of new treatments for endometrial-related disorders.
 Our tools and knowledge have potential to bring preclinical models of the endometrium more firmly into
the realm of humanised research. This work has significant implications for both academic and industrial
research, le...

## Key facts

- **NIH application ID:** 10932965
- **Project number:** 5R01HD114214-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** LINDA G GRIFFITH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $573,160
- **Award type:** 5
- **Project period:** 2023-09-20 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932965

## Citation

> US National Institutes of Health, RePORTER application 10932965, Integrating tissue engineering and microfluidics to model the spatial niches of the human endometrium in vitro with guidance from in vivo multiomics data (5R01HD114214-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10932965. Licensed CC0.

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