期刊
BIOMATERIALS
卷 33, 期 27, 页码 6313-6319出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.05.063
关键词
Human embryonic stem cells; Extracellular matrix; Embryoid bodies; Hypoxia; Cardiomyocytes
资金
- National Science Foundation under NSF award [ECS-0335765]
- MRSEC
- national GEM consortium
- Gates Millennium Scholars Foundation
- Kelly Gene Cook, Sr. Foundation
Limited characterization of how the stern cell niche evolves has hindered our ability to mimic the physiological environment. In this paper, we hypothesized that hypoxia-induced extracellular matrix (ECM) cues may facilitate cardiomyogenesis. We evaluated the expression of four ECM proteins - fibronectin, collagen I, collagen IV, and laminin - over a period of 20 days in H1 and H9 human embryonic stem cell-derived embryoid bodies (EBs) under hypoxic (5% oxygen) and normoxic (21% oxygen) conditions. Hypoxic EBs exhibited increased collagen I, collagen IV and fibronectin expression relative to normoxic EBs between days 9-13, which coincided with increased expression of mesoderm genes. The effect of ECM cues was confirmed by plating day 9 EBs on collagen IV, gelatin, and fibronectin-rich substrates for 11 days. Hypoxia/gelatin cultures synergistically increased the cardiomyocyte yield by 1.7 and 5.5 fold relative to normoxia/gelatin and normoxia/collagen IV cultures, respectively. Current differentiation protocols may underestimate the contribution of hypoxia and ECM cues that evolve during EB maturation. (c) 2012 Elsevier Ltd. All rights reserved.
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