# Dynamics of autocrine and paracrine signaling domains in HSC maintenance

> **NIH NIH F31** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $45,520

## Abstract

Project Summary l
The body’s entire complement of blood and immune cells is produced via hematopoiesis, a process mediated
by a population of hematopoietic stem cells (HSCs). Hematopoietic stem cell transplants (HSCTs), are a common
therapeutic tool for treating malignant and compromised immune and blood systems but have large mortality
rates post-transplant due in part to the inability of the transplanted cells to successfully home and engraft within
the native niche. Inspired by HSCTs, there is an opportunity to develop tools to understand processes associated
with microenvironmental regulation of HSC maintenance and hematopoietic differentiation. Primarily found in the
body’s bone marrow, HSCs exist in temporally and spatially defined regions termed niches that provide key
external cues that direct HSC response. These niches are comprised of mechanical cues, signaling gradients,
and co-inhabiting niche cells, all of which combine to form a vastly complicated system with transitional zones
that promote maintenance, activation, or migration of the inhabiting stem cells. Co-niche inhabiting mesenchymal
stromal cells (MSCs) have been implicated in maintaining HSCs via direct cell-cell contact and secreted factors,
and are significantly involved in remodeling of the surrounding extracellular matrix (ECM), altering the matrix
landscape that the inhabiting HSCs experience. Such matrix remodeling would alter the balance of cell secreted
biomolecular signals surrounding HSCs, notably HSC-mediated autocrine feedback vs. MSC-generated
paracrine signals. Tissue engineering approaches offer an opportunity to study synergies between the dynamic
remodeling of a biomaterial landscape and heterotypic cell-cell interactions mediated by factors secreted by
niche-associated MSCs. To examine the influence of these microenvironmental signals on HSCs maintenance,
HSCs and MSCs will be encapsulated in a series of gelatin hydrogels with defined poroelastic (mechanical,
biotransport) properties. This project will first define HSC maintenance in biomaterial regimes characterized by
the balance of autocrine vs. paracrine dominated signaling, dependent upon the diffusive properties of the gelatin
hydrogel (Aim 1). As MSCs are involved in dynamic remodeling of the hydrogel matrix, we will subsequently
dissect the dynamic contributions of autocrine and paracrine signaling on HSC maintenance in a remodeled
hydrogel matrix (Aim 2). In so doing, we will develop a biomaterial platform to examine dynamic processes
associated with HSC lodgment and maintenance within native marrow niches, and offer design motifs for ex vivo
culture systems to promote maintenance of hematopoietic progenitors.

## Key facts

- **NIH application ID:** 9867522
- **Project number:** 5F31DK117514-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Aidan Gilchrist
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-01-09 → 2021-01-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9867522

## Citation

> US National Institutes of Health, RePORTER application 9867522, Dynamics of autocrine and paracrine signaling domains in HSC maintenance (5F31DK117514-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9867522. Licensed CC0.

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