# Regulation of dental pulp stem cell fate

> **NIH NIH R37** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $390,000

## Abstract

SUMMARY/ABSTRACT
The Problem: The long-term outcome of tissues regenerated with stem cell-based therapies requires functional
vascularization and enervation and a microenvironment that is supportive of the maintenance of undifferentiated
stem cells. In the 1st funding cycle of this project, we demonstrated that neural crest-derived dental pulp stem
cells (DPSC) can differentiate into vascular endothelial cells. In the 2nd cycle, we showed that DPSC-derived
vessels mature upon investment by mural cells and anastomize with host vasculature to become fully functional
blood vessels. During these studies, we observed that a sub-population of DPSCs functions as neural progenitor
cells and differentiate into neural cells while other DPSCs remain undifferentiated via stem cell self-renewal.
Collectively, these tightly modulated events enable the generation of neurovascular stem cell niches in tissues
regenerated with DPSC. However, mechanisms underpinning the generation and maintenance of these niches
are unclear. Therefore, our ability to engage the full potential of DPSCs in tissue regeneration is limited. Premise:
It is known that Brain-Derived Neurotrophic Factor (BDNF) is critical for neurogenic differentiation of progenitor
cells in the central nervous system (CNS) during embryonic development. In contrast, N-Cadherin was shown
to maintain neural progenitor cells in an undifferentiated state in the CNS. Here, we will determine what is the
role of these two signaling pathways in the balance between self-renewal (i.e. maintenance of stemness) and
neurogenic differentiation of neural progenitor cells in the peripheral nervous system using DPSC as a prototypic
mesenchymal stem cell (MSC) population. Further, using single cell RNA sequencing we found that untreated
DPSCs are heterogeneous exhibiting 8 unique cell clusters. Here, we propose studies to understand how DPSC
heterogeneity and plasticity impacts the generation and maintenance of neurovascular stem cell niches in the
pulp. Our overall hypothesis is: “a balance between BDNF-induced neurogenic differentiation and N-Cadherin-
induced self-renewal of neural progenitor cells enables the generation and maintenance of DPSC-derived
neurovascular stem cell niches”. To test this hypothesis, we propose 3 specific aims: S.A.#1: To define the role
of autocrine BDNF on the neurogenic differentiation of DPSC; S.A.#2: To define the role of N-Cadherin signaling
on the maintenance of neural progenitor cells in DPSC-derived neurovascular stem cell niches; S.A.#3: To define
the function of DPSC heterogeneity and plasticity on the generation and maintenance of neurovascular stem cell
niches. Significance: Successful completion of this work will unveil mechanisms that orchestrate the generation
of neurovascular stem cell niches. These niches create a microenvironment that supports the maintenance of
undifferentiated stem cells that can be activated for replacement of dead terminally differentiated cells (e.g.
odont...

## Key facts

- **NIH application ID:** 10878019
- **Project number:** 2R37DE021410-10A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jacques Eduardo Nor
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $390,000
- **Award type:** 2
- **Project period:** 2011-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878019

## Citation

> US National Institutes of Health, RePORTER application 10878019, Regulation of dental pulp stem cell fate (2R37DE021410-10A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10878019. Licensed CC0.

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