# Functional 3D tissue-engineering models of the cerebrovasculature incorporating stem cell-derived brain microvascular endothelial cells, pericytes, and astrocytes

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $339,121

## Abstract

Project Summary
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The neurovasculature supplies nutrients to the 100 billion neurons in the adult human brain via a 600 km
network of capillaries and microvessels. As the interface between the brain and the vascular system, the
blood-brain barrier, which includes the neurovasculature, is responsible for regulating the brain
microenvironment by preventing fluctuations in chemistry, transport of immune cells, and the entry of toxins
and pathogens. At the same time, almost all diseases of the brain are associated with disruption or
dysfunction of the neurovasculature, which leads to entry of blood components, immune cells, and pathogens
into the brain, and ultimately causes neuroinflammation, oxidative stress, and neurotoxicity. Functional human
models have the potential to address many unresolved questions associated with the role of the
neurovasculature in health and disease, and in developing more complex models of the human nervous
system that will ultimately contribute towards the realization of integrated multicellular systems.
There are two major challenges to developing physiologically-relevant, tissue-engineered models of the human
neurovasculature: (1) a source of relevant cells, and (2) 3D cell culture methods to build the model. Stem cell
technology provides a solution to providing a reliable source of human, brain-specific cells, a long-standing
barrier to developing blood-brain barrier models. Similarly, advances in tissue engineering provide the tools for
self-organization of perfusable vascular networks. Solving these problems will have significant impact on
neuroscience research, elucidating mechanisms of central nervous system diseases, and in the development
and translation of new therapies and technologies. In Aim 1 we will characterize the phenotype and barrier
function of brain microvessels under quiescent conditions and in response to activation/stress. In Aim 2 we will
develop and characterize brain-specific capillary networks. In Aim 3 we will integrate pericytes and astrocytes
into our models. These models will enable a broad range of applications, including fundamental studies of
neurogenesis, vascularization, and development, and mechanistic studies of disease progression, treatment,
repair, drug and gene delivery, and toxicity.

## Key facts

- **NIH application ID:** 10075331
- **Project number:** 5R01NS106008-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Peter C Searson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $339,121
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10075331

## Citation

> US National Institutes of Health, RePORTER application 10075331, Functional 3D tissue-engineering models of the cerebrovasculature incorporating stem cell-derived brain microvascular endothelial cells, pericytes, and astrocytes (5R01NS106008-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10075331. Licensed CC0.

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