# Mechanisms of hematopoietic stem cell engraftment

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $453,123

## Abstract

PROJECT SUMMARY/ABSTRACT
 Hematopoietic stem cells (HSCs) possess the ability to replenish a new functional hematopoietic system in
recipients following transplantation and are the only curative treatment for many hematopoietic malignancies and
disorders. However, the availability of donor human leukocyte antigen (HLA)–matched allogeneic HSCs is often
too low for successful transplantation. Haplotype mismatch (or haploidentical) transplantation, where donors are
matched at half of the HLA loci, is an attractive alternative but is limited by increased rejection, often requiring
high-dose immunosuppression to sustain donor grafts. Current clinical transplantation strategies primarily target
the adaptive immune response, however innate immune cells have recently emerged as key actors in the
allograft response in various transplantation models, contributing to both the success and/or rejection of the
transplant. Thus, better understanding of the innate immune response in transplantation and how to target it, is
critical. We have recently discovered a novel function for the HSC niche molecule Vascular Cell Adhesion
Molecule-1 (VCAM1) on HSCs, in which VCAM1 acts as a “don’t-eat-me” signal for innate immune phagocytes
in the context of haplotype mismatch transplantation. Hence, manipulating VCAM1 expression levels may
represent a promising immuno-regulatory approach to control the activity of innate immune cells promoting
haplotype mismatch engraftment. In our first and second aims, we propose to use mouse models of
transplantation to dissect the cellular and molecular mechanisms by which VCAM1 promotes immune evasion
from phagocytes in the context of major histocompatibility complex (MHC)-I presentation. In our third aim, we
will assess the impact of engineering VCAM1 expression levels on donor stem cells in promoting engraftment
across the histocompatibility barrier. This proposal will provide valuable insights in the role of MHC-I engagement
in controlling the function of innate immune cells, and illuminate new molecular targets to improve outcomes in
immunologically mismatched stem cell transplantation assays.

## Key facts

- **NIH application ID:** 10400400
- **Project number:** 1R01HL162584-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Sandra Pinho
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $453,123
- **Award type:** 1
- **Project period:** 2022-04-15 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400400

## Citation

> US National Institutes of Health, RePORTER application 10400400, Mechanisms of hematopoietic stem cell engraftment (1R01HL162584-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10400400. Licensed CC0.

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