# Elucidating the role of pericytes in angiogenesis in the brain using a tissue-engineered microvessel model

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2024 · $245,625

## Abstract

Project Summary
Angiogenesis is a complex and tightly regulated process essential for tissue repair in response to injury or
disease. In the adult human brain, the cerebrovasculature is largely quiescent but angiogenesis is associated
with disease (e.g. stroke, neurodegenerative disease, and brain cancer), wound healing (e.g. traumatic brain
injury), and physiological factors (e.g. exercise, high altitude adaptation, etc.). In the generally accepted model
of brain angiogenesis, when blood vessels are exposed to angiogenic cues, pericytes detach from activated
endothelial cells and are passive bystanders during sprout formation and growth, only migrating back to surround
the newly formed endothelium in the maturation phase. However, a few studies in humans and animal models
have reported that pericytes can play an active role in angiogenesis, leading sprout growth and promoting the
migration of stalk cells.
The objective of this project is to identify the role of pericytes during angiogenesis in the brain. Our major
hypothesis is that pericytes can be selectively activated to become the tip cells and lead the growth of angiogenic
sprouts. The objective will be addressed in three aims. In Aim 1, we will use a tissue-engineered post-capillary
venule model to assess the role of hypoxia and growth factor gradients on pericyte-guided angiogenesis. In Aim
2, we will evaluate the transcriptomic profile of pericytes during angiogenesis. Immunostaining and in situ RNA
hybridization will be used to examine key markers of tip cells as well as to validate key sequencing results. In
Aim 3, we will perform a proof-of-concept experiment to test the hypothesis that gene editing can be used to
engineer tip cell phenotype. Understanding the role of pericytes in adult brain angiogenesis is important in
understanding the response to the cerebrovasculature to a wide range of perturbations and will enable the
development of new therapies for cerebrovascular repair.

## Key facts

- **NIH application ID:** 10805464
- **Project number:** 5R21NS131831-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Peter C Searson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $245,625
- **Award type:** 5
- **Project period:** 2023-03-15 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10805464

## Citation

> US National Institutes of Health, RePORTER application 10805464, Elucidating the role of pericytes in angiogenesis in the brain using a tissue-engineered microvessel model (5R21NS131831-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10805464. Licensed CC0.

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