The use of covalently immobilized stem cell factor to selectively affect hematopoietic stem cell activity within a gelatin hydrogel

被引:87
作者
Mahadik, Bhushan P. [1 ]
Haba, Sara Pedron [2 ]
Skertich, Luke J. [1 ]
Harley, Brendan A. C. [1 ,2 ]
机构
[1] Univ Illinois, Dept Chem & Biomol Engn, Urbana, IL 61801 USA
[2] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA
基金
美国国家科学基金会;
关键词
Bone marrow; Stem cell; Cell activation; Hydrogel; Growth factor; EX-VIVO EXPANSION; FOCAL ADHESION KINASE; BONE-MARROW; PROGENITOR CELLS; NICHE; SCAFFOLDS; INTERNALIZATION; VIABILITY; PROTEINS; CULTURE;
D O I
10.1016/j.biomaterials.2015.07.042
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
收藏
页码:297 / 307
页数:11
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