# In vivo two-photon imaging of vascular invasion and stem cell translocation in calvarial bone

> **NIH NIH R21** · SEATTLE CHILDREN'S HOSPITAL · 2024 · $246,125

## Abstract

PROJECT SUMMARY
Calvarial bone defects commonly occur as a result of trauma, congenital anomalies and iatrogenic conditions.
The healing of bone defects relies on the regenerative capability of calvarial bones to replace damaged bone
tissues and the availability of skeletal stem cells (SSCs) is one of the key factors for generating new bones to
restore both structural and functional integrity. Calvarial SSCs that express marker gene Gli1, Axin2 or Prx1
reside in the sutural stem cell niche and contribute to calvarial bone homeostasis and healing after injury. It
remains unclear how calvarial SSCs translocate from the sutural niche to distant regions of the calvarial bones
for bone repair after injury of sites remote to the suture. Our preliminary analysis through 2-photon imaging
indicates that Gli1-expressing calvarial SSCs not only reside in the sutural niche but also line the walls of blood
vessels distributed widely throughout the postnatal calvarial bones. In this project, we will test the hypothesis
that calvarial SSCs in the sutural niche could translocate with vascular invasion that initiates at the postnatal
suture, and could reside within calvarial bones to contribute to bone regeneration after injury. We propose two
specific aims for this project: 1) Determine if vascular invasion from the suture results in bone marrow cavity
formation in postnatal calvarial bones, and 2) Determine if calvarial SSCs in the sutural niche translocate with
vascular invasion to establish the SSC niche in bone marrow cavities of postnatal calvarial bones. This
research proposal leverages the unique expertise of two investigative labs to address a key gap in our
knowledge of calvarial healing. Successful completion of this exploratory research will set the stage for further
mechanistic studies such as molecular regulation of calvarial SSC translocation, which could facilitate the
development of new therapeutic approaches for rapid bone regeneration after injury.

## Key facts

- **NIH application ID:** 10828352
- **Project number:** 5R21DE031942-02
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Andy Y Shih
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $246,125
- **Award type:** 5
- **Project period:** 2023-05-01 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10828352

## Citation

> US National Institutes of Health, RePORTER application 10828352, In vivo two-photon imaging of vascular invasion and stem cell translocation in calvarial bone (5R21DE031942-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10828352. Licensed CC0.

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