# Ex vivo analysis of human brain tumor cells in a microvascular niche model

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $546,939

## Abstract

PROJECT SUMMARY
The region near the brain vasculature in human brain tumors, called the perivascular niche (PVN), is an
important microenvironment for the maintenance of brain tumor stem-like cells (BTSCs), the development of
resistance to chemo or targeted therapies, and the path for tumor infiltration to distant regions in the whole
brain, leading to incurable diseases. Current in vitro models such as 2D cell cultures or 3D tumor spheroids do
not contain this niche environment. Mouse models of brain tumors can recapitulate some aspects of the PVN,
but have challenges in terms of costly assays, low throughput, and lack of the ability for high-resolution live cell
tracking of BTSC dynamics. Herein, we propose to develop a tissue-engineered 3D microvascular niche-on-a-
chip model that can incorporate primary brain tumor cells from patients in order to bridge this gap between in
vitro and in vivo models. Our pilot study has demonstrated the success in co-culture of patient-derived
glioblastoma cells and microvasculature in a microfluidic gel system and observed preferential localization of
BTSCs in the PVN. Comparing ex vivo dynamics of individual tumor cells on-chip to single-cell transcriptomes
across 10 patients further revealed a correlation between perivascular localization and transcriptional subtypes.
In this project, we propose to further examine tumor cell migration and localization using a larger cohort of
patient specimens and compare the results to pathological and clinical data, aiming to develop it into an ex vivo
functional assay for patient prognosis and subclassification (Aim 1). We will apply scRNA-seq to the same
samples to generate correlative data to identify subtypes associated with distinct ex vivo dynamics in the
tissue-engineered PVN model, which can help elucidate the molecular mechanisms of PVN in tumor cell fate
and invasion (Aim 2). Finally, we will investigate the response of tumor cells in PVN to chemo and targeted
therapies administered through the perfusable microvascular network to assess the potential to perform
personalized drug test and therapeutic stratification (Aim 3). This project will lead to a novel tissue-engineered
microsystem to not only study the biology of PVN in human brain tumor development but also develop new
assays for ex vivo test of human tumor cells for precision medicine.

## Key facts

- **NIH application ID:** 10098019
- **Project number:** 5R01CA245313-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Rong Fan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $546,939
- **Award type:** 5
- **Project period:** 2020-02-04 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10098019

## Citation

> US National Institutes of Health, RePORTER application 10098019, Ex vivo analysis of human brain tumor cells in a microvascular niche model (5R01CA245313-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10098019. Licensed CC0.

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