# Microvascular Permeability, Inflammation, and Lesion Physiology in Endometriosis: A Microphysiological Systems Approach

> **NIH NIH U01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $587,338

## Abstract

Project Summary
The endometrium is a complex mucosal barrier that lines the uterine muscle and undergoes a
remarkable, hormonally-driven scarless healing process to regenerate the ~1 cm thick
functionalis layer, which, absent embryo implantation, is shed each month from the permanent
stem cell-containing basalis layer. This process is a source of tragic illness for an estimated
200 million girls and women worldwide who suffer debilitating pain and infertility from chronic
diseases in which the endometrium grows ectopically, in the myometrium (adenomyosis) or
outside the uterus, invading deep into abdominal organs and migrating throughout the body
(endometriosis). Ectopic lesions undergo cyclic hormonally-induced changes that cause local
bleeding and inflammation, leading to progressive invasion and fibrosis and growth of lesions
from small (~0.1mm) epithelial acinar structures with associated stroma, to large (~ cm) fibrotic
lesions. Animal models do not capture the spectrum of behaviors of the human condition.
Therefore, we propose to build a microphysiological system (MPS) model of early-stage lesions.
In the first phase of the project, we integrate 3 independent MPS platform technologies to solve
outstanding technical problems in modeling metabolically-active tissues where microvasculature
and inflammation (extravasation of circulating immune cells to form tissue-resident cells) are
crucially involved, incorporating a previously-developed tissue engineered static model of
endometrium and endometrial lesions. After validating the platform performance and basic
MPS function, we then compare the behavior of lesions with different properties. A major
emphasis of this work is characterizing how reproducible the outcomes are within a single
donor, and the variation among donors. A second major emphasis is gaining quantitative
insights into inflammatory cell-cell communication networks in MPS systems. We use the
platform for 3 Aims: AIM 1 - Define the range of phenotypic responses and molecular signatures
for lesions as a function of donor status and hormonal cycle status, determining factors that
influence the reproducibility for repeated experiments with the same donor, and those between
donors AIM 2 – Evaluate how lesions recruit circulating monocytes immune cells in a hormone
cycle-dependent manner, and characterize the evolution of recruited monocyte phenotype in
tissues as a function of donor state, in terms of cytokine signatures. AIM 3 – Evaluate of lesion
responses to established and experimental therapies as a function of lesion progression state
and donor cell hormonal response status.

## Key facts

- **NIH application ID:** 10021406
- **Project number:** 5U01EB029132-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** LINDA G GRIFFITH
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $587,338
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10021406

## Citation

> US National Institutes of Health, RePORTER application 10021406, Microvascular Permeability, Inflammation, and Lesion Physiology in Endometriosis: A Microphysiological Systems Approach (5U01EB029132-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10021406. Licensed CC0.

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