# Improving the interaction of hematopoietic stem cells with the perivascular niche to promote engraftment

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $474,652

## Abstract

PROJECT SUMMARY/ABSTRACT
Hematopoietic stem cell (HSC) transplantation is a curative treatment for many blood diseases and cancers.
However, these procedures still need to be optimized to improve patient outcomes and survival. In part, we have
been limited by our poor understanding of how donor HSCs interact with the recipient bone marrow after
transplantation. This research proposal seeks to address fundamental questions regarding the cellular
interactions between HSCs and niche cells. Based on our previous data, we have shown that the niche not
only instructs HSC, but that HSC also transmit instructive cues to the niche. These include triggered
remodeling of surrounding endothelial cells into a supportive pocket that “cuddles” the HSC. To better describe
this novel cellular structure, we combined multiple imaging modalities to produce the first correlative light and
electron microscopy data of an endogenous stem cell in its niche. We have since performed functional genetic
studies that provided mechanistic insight into the formation of this structure. These preliminary results have led
us to pursue the following Specific Aims: 1) Identify the HSC-derived paracrine signals that mediate EC
remodeling to form a niche for HSCs; 2) Identify mechanisms of adhesive HSC-EC niche interactions
that promote signaling and stable expansion of the HSC pool. We will perform in vivo genetic knockdown
and small molecule treatments, together with live imaging, to understand the dynamic interactions between HSC
and endothelial cells. We will then translate these results to an in vitro vascular niche with the potential to expand
HSCs prior to transplantation. Ultimately, we hope our studies will lead to improved clinical HSC transplantation
protocols.

## Key facts

- **NIH application ID:** 10240737
- **Project number:** 5R01HL142998-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Owen James Tamplin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $474,652
- **Award type:** 5
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240737

## Citation

> US National Institutes of Health, RePORTER application 10240737, Improving the interaction of hematopoietic stem cells with the perivascular niche to promote engraftment (5R01HL142998-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10240737. Licensed CC0.

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