# Human neural stem cell and endothelial cell reciprocal interactions govern cell function

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $392,500

## Abstract

Project Summary
Neural stem/progenitor cells (NSPCs) lie in close proximity to blood vessels in brain stem cell
niches and after transplant to treat neurological conditions. This adjacency allows for
considerable interaction between NSPCs and the endothelial cells (ECs) that form blood
vessels, creating an interdependent and complex relationship between these cell types. Human
NSPC (hNSPC) and human EC (hEC) interactions have not been well studied, creating
knowledge gaps that hinder our understanding of human brain function and repair after injury.
We used a tissue engineering approach with a a 3D scaffold mimicking brain properties to study
hNSPC-hEC interactions. We found hEC contact with hNSPCs induced the formation of GFAP+/
SOX2+ cells, which could be type B adult neural stem cells. Type B cells are slowly dividing
NSPCs that prevent depletion of the NSPC pool and may be activated after injury to help
replace lost brain cells. We found hNSPCs stimulate hEC vessel formation (vasculogenesis)
and this effect is mediated by hNSPC secreted components rather than hNSPC contact with
hECs. These data lead to the hypothesis that hEC contact promotes a type B adult neural
stem cell phenotype while hNSPC secreted components stimulate human vessel
formation in 3D niches.
We will test this hypothesis with the following Aims: Aim 1 - determine how contact with hECs
affects hNSPCs; Aim 2 - determine how hNSPC secreted components impact human vessels;
Aim 3 - test whether hNSPCs and hECs promote type B adult neural stem cells and vessels in
vivo. By investigating the crucial interactions between hNSPCs and hECs in 3D tissue
engineered niches, we will better understand how their relationship impacts human brain
function. This knowledge could be used in the future to optimize co-transplants of hNSPCs and
hECs in scaffolds to recreate critical niche interactions leading to formation of type B cells and
vessels that stimulate brain repair.

## Key facts

- **NIH application ID:** 10299367
- **Project number:** 1R01NS119829-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** LISA A FLANAGAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $392,500
- **Award type:** 1
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10299367

## Citation

> US National Institutes of Health, RePORTER application 10299367, Human neural stem cell and endothelial cell reciprocal interactions govern cell function (1R01NS119829-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10299367. Licensed CC0.

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