# Gradient biomaterials to investigate niche regulation of hematopoiesis > **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2024 · $548,805 ## Abstract ABSTRACT The hematopoietic system offers an ideal biological system to develop tools to study how dynamic matrix, metabolic, and cellular selection pressures influence stem cell fate. Hematopoiesis is the process where the body’s blood and immune cells are generated from a small number of hematopoietic stem cells (HSCs). HSC quiescence, self-renewal, and differentiation take place in, and are regulated by, unique regions of the bone marrow termed niches. HSCs are also the functional unit of therapeutic bone marrow transplants following myeloablative therapies. A major goal of the hematology community is to selectively expand HSCs without sacrificing a subpopulation of quiescent, long-term repopulating HSCs required for life-long hematopoiesis. Yet while the marrow is known to change substantially across the lifespan, studies of the influence of niche remodeling on HSC behavior are in their infancy. The long-term goal of this Stimulating Hematology Investigation New Endeavors (SHINE) project is to advance tissue engineering platforms to achieve HSC expansion without exhaustion. In the previous funding period (R01DK099528) we established a tissue engineering ecosystem to examine the coordinated impact of niche-inspired biophysical signals on HSC fate. We developed microfluidic tools for extended culture of primary murine HSC in miniaturized gelatin hydrogels containing marrow-inspired gradients of stiffness, niche cells, and soluble vs. immobilized biomolecules We showed the kinetics of HSC- niche cell crosstalk can be manipulated via biomaterial design to enhance retention of quiescent HSCs. Mesenchymal stem cells (MSCs) within the marrow are increasingly believed to dynamically remodel the niche and provide powerful signals to influence HSC fate. Hence, the objective of our renewal is to use an innovative granular biomaterial to investigate the coordinated action of MSC remodeling and hypoxic stress on functional changes in HSC activity. We hypothesize the mosaic nature of the bone marrow can be replicated as jammed assemblies of cell-laden hydrogel microdroplets. We will create granular hydrogels from MSC and HSC microdroplets to trace the consequences of matrix remodeling, metabolic constraint, and MSC-HSC crosstalk on HSC fate. To accomplish this goal we will first establish an engineered model of MSC-mediated niche remodeling (Aim 1). We will define shifts in HSC-MSC crosstalk under hypoxia (Aim 2). And we will evaluate a mosaic granular hydrogel model of the multicellular marrow (Aim 3). Granular hydrogels provide the technical basis for creating mosaic niche analogs necessary to study remodeling mediated effects on HSC activity. The well- characterized murine hematopoietic system provides a rigorous framework to evaluate ex vivo regulatory processes in niches whose rarity and complexity limit direct in vivo study. Consistent with score-driving criteria of the SHINE program, we will develop essential tools to rigorously assess how dynamic pr... ## Key facts - **NIH application ID:** 10886103 - **Project number:** 5R01DK099528-07 - **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN - **Principal Investigator:** Brendan A. Harley - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $548,805 - **Award type:** 5 - **Project period:** 2014-08-01 → 2027-04-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10886103 ## Citation > US National Institutes of Health, RePORTER application 10886103, Gradient biomaterials to investigate niche regulation of hematopoiesis (5R01DK099528-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10886103. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*