Journal
BIOMATERIALS
Volume 67, Issue -, Pages 297-307Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.07.042
Keywords
Bone marrow; Stem cell; Cell activation; Hydrogel; Growth factor
Funding
- National Science Foundation [1254738]
- NIH [R01 DK099528]
- Illini 4000
- American Cancer Society, Illinois Division, Inc. [189782]
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1254738] Funding Source: National Science Foundation
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Hematopoietic stem cells (HSCs) are a rare stem cell population found primarily in the bone marrow and responsible for the production of the body's full complement of blood and immune cells. Used clinically to treat a range of hematopoietic disorders, there is a significant need to identify approaches to selectively expand their numbers ex vivo. Here we describe a methacrylamide-functionalized gelatin (GelMA) hydrogel for in vitro culture of primary murine HSCs. Stem cell factor (SCF) is a critical biomolecular component of native HSC niches in vivo and is used in large dosages in cell culture media for HSC expansion in vitro. We report a photochemistry based approach to covalently immobilize SCF within GelMA hydrogels via acrylate-functionalized polyethylene glycol (PEG) tethers. PEG-functionalized SCF retains the native bioactivity of SCF but can be stably incorporated and retained within the GelMA hydrogel over 7 days. Freshly-isolated murine HSCs cultured in GelMA hydrogels containing covalently-immobilized SCF showed reduced proliferation and improved selectivity for maintaining primitive HSCs. Comparatively, soluble SCF within the GelMA hydrogel network induced increased proliferation of differentiating hematopoietic cells. We used a microfluidic templating approach to create GelMA hydrogels containing gradients of immobilized SCF that locally direct HSC response. Together, we report a biomaterial platform to examine the effect of the local presentation of soluble vs. matrix-immobilized biomolecular signals on HSC expansion and lineage specification. This approach may be a critical component of a biomaterial-based artificial bone marrow to provide the correct sequence of niche signals to grow HSCs in the laboratory. (C) 2015 Elsevier Ltd. All rights reserved.
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