TY - JOUR
T1 - Influence of Hypoxia on a Biomaterial Model of the Bone Marrow Perivascular Niche
AU - Thompson, Gunnar B.
AU - Barnhouse, Victoria R.
AU - Bierman, Sydney K.
AU - Harley, Brendan A.C.
N1 - Funding sources include the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number 2 R01 DK099528, the National Institute of Dental and Craniofacial Research of the National Institutes of Health under Award Number R01 DE030491, and the National Cancer Institutes of the National Institutes of Health under Award Number R01 CA256481. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors are also grateful for additional funding provided by the Department of Chemical & Biomolecular Engineering, Department of Bioengineering, the Carl R. Woese Institute for Genomic Biology, the Cancer Center at Illinois, and the Illinois Scholars Undergraduate Research Program at the University of Illinois Urbana\u2010Champaign. The authors wish to thank the Roy J. Carver Biotechnology center, Cytometry and Microscopy to Omics Facility ( RRID:SCR_025272 \u2010 https://coremarketplace.org/?FacilityID = 2727) for providing expertise in Cytometry/Sorting, Microscopy and Omics analysis for the project. Specifically, the authors would like to thank Dr. Mayandi Sivaguru and Dr. Marcin Wozniak for their assistance with cell sorting. The authors also wish to thank the Core Facilities at the Carl R. Woese Institute for Genomic Biology for use of their LSM710 and LSM880 microscopes. In particular, the authors would like to thank Dr. Austin J. Cyphersmith and Dr. Duncan Nall for training and imaging assistance. FiguresA 1A, 4A , 5A , and 6A were created with BioRender.com.
PY - 2025/5/28
Y1 - 2025/5/28
N2 - Hematopoietic stem cell (HSC) fate is shaped by distinct microenvironments termed niches within the bone marrow. Quiescence, expansion, and differentiation are directly and indirectly regulated by complex combinations of cell secretomes, cell-cell interactions, mechanical signals, and metabolic factors including oxygen tension. The perivascular environment in the bone marrow has been implicated in guiding HSC fate. However, bone marrow presents an environment which is hypoxic (≈1-4% O2) relative to traditional cell culture conditions, and the study of hypoxia in vitro is complicated by the speed with which normoxic conditions during HSC isolation induce differentiation. There is a unique opportunity to use engineered models of the bone marrow to investigate the impact of defined hypoxia on HSC fate. Here, the coordinated impact of oxygen tension and the perivascular secretome upon murine hematopoietic stem and progenitor cells (HSPCs) is examined in vitro. The findings highlight the importance of mitigating oxygen shock during cell isolation in engineered marrow models. We report a shift toward the Lineage− phenotype with hypoxic culture, expansion of HSPCs in response to perivascular niche conditioned medium, and enhanced HSPC maintenance in a hydrogel model of bone marrow in hypoxic culture when oxygen shock is mitigated during isolation using cyclosporin A.
AB - Hematopoietic stem cell (HSC) fate is shaped by distinct microenvironments termed niches within the bone marrow. Quiescence, expansion, and differentiation are directly and indirectly regulated by complex combinations of cell secretomes, cell-cell interactions, mechanical signals, and metabolic factors including oxygen tension. The perivascular environment in the bone marrow has been implicated in guiding HSC fate. However, bone marrow presents an environment which is hypoxic (≈1-4% O2) relative to traditional cell culture conditions, and the study of hypoxia in vitro is complicated by the speed with which normoxic conditions during HSC isolation induce differentiation. There is a unique opportunity to use engineered models of the bone marrow to investigate the impact of defined hypoxia on HSC fate. Here, the coordinated impact of oxygen tension and the perivascular secretome upon murine hematopoietic stem and progenitor cells (HSPCs) is examined in vitro. The findings highlight the importance of mitigating oxygen shock during cell isolation in engineered marrow models. We report a shift toward the Lineage− phenotype with hypoxic culture, expansion of HSPCs in response to perivascular niche conditioned medium, and enhanced HSPC maintenance in a hydrogel model of bone marrow in hypoxic culture when oxygen shock is mitigated during isolation using cyclosporin A.
KW - gelatin
KW - hematopoietic stem cells
KW - hydrogel
KW - hypoxia
KW - perivascular niche
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U2 - 10.1002/adhm.202500858
DO - 10.1002/adhm.202500858
M3 - Article
C2 - 40285591
AN - SCOPUS:105003826483
SN - 2192-2640
VL - 14
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 14
M1 - 2500858
ER -