Perivascular Secretome Influences Hematopoietic Stem Cell Maintenance in a Gelatin Hydrogel
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Annals of Biomedical Engineering ( 2020) https://doi.org/10.1007/s10439-020-02602-0
Original Article
Perivascular Secretome Influences Hematopoietic Stem Cell Maintenance in a Gelatin Hydrogel VICTORIA BARNHOUSE,1 NATHAN PETRIKAS,2,3 CODY CROSBY,4 JANET ZOLDAN,4 and BRENDAN HARLEY 2,3 1
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; 2Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 110 Roger Adams Laboratory, Urbana, IL 61801, USA; 3Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; and 4 Department of Biomedical Engineering, University of Texas at Austin, Austin, USA (Received 25 April 2020; accepted 2 September 2020) Associate Editor Jennifer West oversaw the review of this article.
Abstract—Adult hematopoietic stem cells (HSCs) produce the body’s full complement of blood and immune cells. They reside in specialized microenvironments, or niches, within the bone marrow. The perivascular niche near blood vessels is believed to help maintain primitive HSCs in an undifferentiated state but demonstration of this effect is difficult. In vivo studies make it challenging to determine the direct effect of the endosteal and perivascular niches as they can be in close proximity, and two-dimensional in vitro cultures often lack an instructive extracellular matrix environment. We describe a tissue engineering approach to develop and characterize a three-dimensional perivascular tissue model to investigate the influence of the perivascular secretome on HSC behavior. We generate 3D endothelial networks in methacrylamide-functionalized gelatin hydrogels using human umbilical vein endothelial cells (HUVECs) and mesenchymal stromal cells (MSCs). We identify a subset of secreted factors important for HSC function, and examine the response of primary murine HSCs in hydrogels to the perivascular secretome. Within 4 days of culture, perivascular conditioned media promoted maintenance of a greater fraction of hematopoietic stem and progenitor cells. This work represents an important first-generation perivascular model to investigate the role of niche secreted factors on the maintenance of primary HSCs. Keywords—Tissue engineering, Biomaterial niche, Hematopoietic stem cell.
Address correspondence to Brendan Harley, Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 110 Roger Adams Laboratory, Urbana, IL 61801, USA. Electronic mail: [email protected]
INTRODUCTION Adult hematopoietic stem cells (HSCs) reside in the bone marrow and are responsible for producing the body’s full complement of blood and immune cells through a process termed hematopoiesis.6 Clinically, HSCs are used to treat a number of hematological disorders including leukemia and lymphoma via transplantation of donor HSCs from either autologous, allogenic, or umbilical cord blood sources into the patient after successful ablation of the patient’s bone marrow.13,21 H
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