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Nat Mater. 2016 Mar;15(3):344-52. doi: 10.1038/nmat4536. Epub 2016 Jan 11.

Defined three-dimensional microenvironments boost induction of pluripotency.

Author information

1
Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV) and School of Engineering (STI), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
2
School of Life Sciences, Core Facility PTECH, EPFL, 1015 Lausanne, Switzerland.
3
Institute of Chemical Sciences and Engineering, School of Basic Science (SB), EPFL, 1015 Lausanne, Switzerland.

Abstract

Since the discovery of induced pluripotent stem cells (iPSCs), numerous approaches have been explored to improve the original protocol, which is based on a two-dimensional (2D) cell-culture system. Surprisingly, nothing is known about the effect of a more biologically faithful 3D environment on somatic-cell reprogramming. Here, we report a systematic analysis of how reprogramming of somatic cells occurs within engineered 3D extracellular matrices. By modulating microenvironmental stiffness, degradability and biochemical composition, we have identified a previously unknown role for biophysical effectors in the promotion of iPSC generation. We find that the physical cell confinement imposed by the 3D microenvironment boosts reprogramming through an accelerated mesenchymal-to-epithelial transition and increased epigenetic remodelling. We conclude that 3D microenvironmental signals act synergistically with reprogramming transcription factors to increase somatic plasticity.

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PMID:
26752655
DOI:
10.1038/nmat4536
[Indexed for MEDLINE]

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