# Matching panels of in vivo and in vitro model system of pediatric brain tumors

> **NIH NIH U01** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2020 · $897,346

## Abstract

Project Summary
Brain tumors are the leading cause of cancer-related death in children. Poor understanding of the interactions
between tumor cells, especially cancer stem cells (CSCs), and normal brain tissues have played a role. Due to
the difficulties of obtaining tumor tissues, there is a limited availability of biologically accurate and matched in
vitro (tumor organoid) and in vivo (PDOX) model systems. Normal brain tissue is more difficult to obtain, making
it nearly impossible to develop normal brain organoids. To overcome these barriers, we propose to utilize our
existing (n=127) and future established patient derived orthotopic xenograft (PDOX) models as the source supply
of tumor cells to develop matching tumor organoids. These PDOX models replicate the biology of original patient
tumors and represent a wide spectrum of the newly discovered molecular subtypes of malignant brain tumors.
Using 24 PDOX models, we have established 13 (54.1%) tumor organoids. Recognizing the rarity of normal
brain tissues, we propose to use autopsied tissues. Indeed, we have cryopreserved viable cells of normal
cerebrum, cerebellum, brain stem, and sub-ventricular zone cells from children of different ages and showed
that the autopsied cerebral cells can proliferate in vitro to form neurospheres. We, therefore, hypothesize that 1)
autopsied normal brain tissues and PDOX models can provide critically needed and biologically accurate cells
for the development of normal and tumor organoid, and 2) the growth of these organoid are dependent on the
growth factor milieu of their location and modulated by the dynamic interactions between different types of cells.
Radiation therapy is one of the most important treatment regimens for pediatric brain tumors. Since mutation of
histone modification genes are frequent in pediatric brain tumors, our 3rd hypothesis is that such epigenetic
changes affect responses and resistance toward radiation, and successful targeting in organoid and PDOX
tumors will lead to new combination therapies. We propose three Specific Aims. Aim 1: Develop normal brain
organoids from autopsied normal cerebrum, cerebellum, brain stem and subventricle zone from all age groups
and establish tumoral organoids from PDOX models and identify their location- and developmental-stage
dependent niche factor combinations, respectively. Aim 2: Understand the dynamic interactions between tumor
(CSCs and non-stem tumor) cells and normal brain cells. We will use co-culture assays to identify the niche
factor combinations that dictate cellular diversity and survival of CSC and normal brain cells, and perform global
multi-omics analysis and single cell RNAseq to elucidate the molecular mechanisms, followed by in vivo
validation of our findings in PDOX models. Aim 3: Determine the role of histone methylation in regulating CSC
survival and self-renewal of malignant brain tumors when perturbed by radiation. We will use normal and tumoral
organoids to determine how pre-...

## Key facts

- **NIH application ID:** 9888891
- **Project number:** 1U01CA217613-01A1
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** Xiaonan Li
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $897,346
- **Award type:** 1
- **Project period:** 2020-03-03 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9888891

## Citation

> US National Institutes of Health, RePORTER application 9888891, Matching panels of in vivo and in vitro model system of pediatric brain tumors (1U01CA217613-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9888891. Licensed CC0.

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