# REGULATION OF BONE MARROW MESENCHYMAL STEM CELLS BY VCAM1

> **NIH NIH F31** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $40,471

## Abstract

ABSTRACT
Hematopoietic stem cells (HSCs) are rare cells that reside in the bone marrow (BM) where they are maintained
by specialized microenvironments (termed niches) in which endothelial, stromal, and other hematopoietic cells
synthesize important niche factors that regulate HSC function. Mesenchymal stem cells (MSCs) are an essential
component of the BM niche. These rare non-hematopoietic perivascular stromal cells are characterized by their
unique ability to self-renew and differentiate into bone, cartilage, and fat, ensuring proper skeletal development
and maintenance. BM MSCs form specialized niches that regulate HSC function by secreting high levels of niche
factors such as CXC-chemokine ligand 12 (CXCL12), stem cell factor (SCF), and Vascular Cell Adhesion
Molecule-1 (VCAM1). VCAM1 is classically expressed on endothelial and stromal cells where it acts as an
adhesion molecule that preferentially binds to α4β1 integrin on HSCs and progenitors. Deletion of Vcam1 in
endothelial and hematopoietic cells induces HSC and progenitor cell (HSPC) mobilization into the peripheral
blood without affecting endothelial cell (EC) homeostasis. However, while the contribution of endothelial-derived
VCAM1 to BM homeostasis has been extensively studied, the specific role of MSC-derived VCAM1 on HSC and
on MSC maintenance and multilineage potency remains unknown. Our supporting data indicates that MSCs are
the BM’s main source of Vcam1 and suggests that VCAM1 is critical for the maintenance, survival, and function
of MSCs. Since MSCs are important regulators of HSC function and essential for skeleton and BM stroma
formation and maintenance, it is critical to understand the extent at which MSC-derived Vcam1 deletion impacts
MSCs and hematopoietic homeostasis. Based on our supporting data, I hypothesize that MSC-derived VCAM1
expression is critical for MSC maintenance and niche functions. The overall aims of this project are to
elucidate the mechanisms by which VCAM1 promotes MSC survival and regulates HSPC function. Altogether,
our proposal will provide mechanistic evidence for VCAM1 as a novel regulator of MSCs. While the critical
regulators of HSC maintenance and differentiation have been intensively studied, that of BM niche MSCs still
remain largely unknown. Our studies will not only aid in our understanding of MSCs but also the mechanisms
encompassing HSC maintenance to ultimately help improve treatments for hematopoietic diseases.

## Key facts

- **NIH application ID:** 10537391
- **Project number:** 1F31HL165859-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Anna Marisa Di Staulo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $40,471
- **Award type:** 1
- **Project period:** 2023-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537391

## Citation

> US National Institutes of Health, RePORTER application 10537391, REGULATION OF BONE MARROW MESENCHYMAL STEM CELLS BY VCAM1 (1F31HL165859-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10537391. Licensed CC0.

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