# Modeling Anthracycline-Induced Cognitive Impairment Using iPSC-Derived Brain-On-Chips

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $393,607

## Abstract

PROJECT SUMMARY
Doxorubicin (DOX), a well-established and highly effective chemotherapy drug of the anthracycline class, is
commonly used to treat multiple malignancies. Accumulating evidence shows that cancer patients who
underwent anthracycline-based chemotherapy showed more severe cognitive impairment than those who
received non-anthracycline regimens. However, due to the relative inaccessibility of functional human brain
tissues for research, the underlying mechanisms of DOX-induced cognitive impairment remain poorly
understood. To that end, in this Alzheimer’s-focused administrative supplement, we aim to use patient-specific
induced pluripotent stem cell (iPSC)-derived neurovascular cells in 2D and 3D cultures to model this diseased
phenotype in a dish. In Aim 1, we will generate iPSC-brain pericytes and iPSC-brain microvascular endothelial
cells (BMECs) from 10 DOX-insensitive and 10 DOX-sensitive patients, and test cell viability, oxidative stress,
mitochondrial function, and cytokine secretion in both vascular cell types before and after physiological DOX
treatment. In Aim 2, we will use brain-on-chips to generate an in vitro 3D blood-brain barrier-like structure (the
neurovascular unit) comprising of isogenic iPSC-pericytes, iPSC-BMECs, iPSC-astrocytes, and iPSC-neurons
as a more physiological relevant platform to investigate the effects of cell-cell interaction on DOX-induced BBB
integrity disruption. Overall, the platform we will be establishing can serve as a proof-of-principle to test druggable
targets that can ameliorate cognitive deficits or various types of neurodegenerative diseases caused by cancer-
related treatments.

## Key facts

- **NIH application ID:** 10283208
- **Project number:** 3R01HL123968-08S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** THOMAS QUERTERMOUS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $393,607
- **Award type:** 3
- **Project period:** 2014-08-05 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10283208

## Citation

> US National Institutes of Health, RePORTER application 10283208, Modeling Anthracycline-Induced Cognitive Impairment Using iPSC-Derived Brain-On-Chips (3R01HL123968-08S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10283208. Licensed CC0.

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