Journal
BIOMATERIALS
Volume 34, Issue 4, Pages 912-921Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.10.020
Keywords
Human pluripotent stem cells; Embryonic stem cells; Self-renewal; Synthetic matrices; Physicochemical cues; Synthetic heparin mimics
Funding
- California Institute of Regenerative Medicine [RN2-00945, RT2-01889]
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Cost-effective and scalable synthetic matrices that support long-term expansion of human pluripotent stem cells (hPSCs) have many applications, ranging from drug screening platforms to regenerative medicine. Here, we report the development of a hydrogel-based matrix containing synthetic heparin-mimicking moieties that supports the long-term expansion of hPSCs (>= 20 passages) in a chemically defined medium. HPSCs expanded on this synthetic matrix maintained their characteristic morphology, colony forming ability, karyotypic stability, and differentiation potential. We also used the synthetic matrix as a platform to investigate the effects of various physicochemical properties of the extracellular environment on the adhesion, growth, and self-renewal of hPSCs. The observed cellular responses can be explained in terms of matrix interface-mediated binding of extracellular matrix proteins, growth factors, and other cell-secreted factors, which create an instructive microenvironment to support self-renewal of hPSCs. These synthetic matrices, which comprise of off-the-shelf components and are easy to synthesize, provide an ideal tool to elucidate the molecular mechanisms that control stem cell fate. (C) 2012 Elsevier Ltd. All rights reserved.
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