# Enhanced cellular therapy for neonatal stroke

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $352,005

## Abstract

PROJECT SUMMARY
Neonatal stroke is an important cause of death and disability, resulting from multiple pathways of cell death
and dysfunction that evolve over a prolonged period of time. There is insufficient knowledge regarding the role
of angiogenesis in the response to focal ischemia-reperfusion injury that is the most common cause of early
stroke. Angiogenesis and neuronal repopulation occur in close proximity, with paracrine factors supporting
neuron-endothelial cell interactions that are critical for repair. Modulating this neurovascular niche may be a
potential target for enhancing outcomes after ischemic brain injury in the newborn period. Cell-based therapies
have emerged as a promising treatment for CNS disease, although the mechanism of repair has been
controversial. Mesenchymal stem cells (MSC) play a role in vascular formation and secrete pro-angiogenic
factors, express a number of growth factor receptors, and may preferentially differentiate into cells capable of
building new blood vessels after injury. MSC treatment has been shown to improve histological and functional
outcomes after ischemic injury, even when therapy was delayed, but it is only partially reparative. Modifying
MSC in a way that enhances effects on the neurovascular unit may provide additional benefit.
Our overall objective is to determine the mechanism of regeneration and repair with delayed cellular therapy
for neonatal stroke by focusing on the vascular response in the injured brain. In Aim 1, we will test the
hypothesis that MSC pre-exposed to EPO will enhance angiogenesis and vascular remodeling following
neonatal focal ischemia-reperfusion injury in the rat more than MSC or EPO therapy alone. In Aim 2, we will
clarify to what extent this modified cellular therapy modulates long-term repair by using a number of techniques
to quantify cell fate, gross histology and long-term sensorimotor and cognitive outcomes. Finally, in Aim 3, we
will define the roles of specific downstream signaling pathways on angiogenesis and repair following ischemia-
reperfusion injury and cellular therapy. This will determine critical, modifiable pathways important for
angiogenesis in the developing brain and following focal injury, which can be further studied to enhance long-
term repair. Our primary hypothesis is that delayed treatment with MSC pretreated with EPO will promote
vascular growth and remodeling, increase neurogenesis, and improve long-term histological and functional
outcomes after neonatal stroke. This will provide a late treatment option for a common cause of early brain
injury, where diagnosis is often delayed.

## Key facts

- **NIH application ID:** 9830703
- **Project number:** 5R01NS107039-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Fernando Francisco Gonzalez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,005
- **Award type:** 5
- **Project period:** 2017-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830703

## Citation

> US National Institutes of Health, RePORTER application 9830703, Enhanced cellular therapy for neonatal stroke (5R01NS107039-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9830703. Licensed CC0.

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