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.
Nat Mater. 2016 Mar;15(3):344-52
Caiazzo M, Okawa Y, Ranga A, Piersigilli A, Tabata Y, Lutolf MP.
Curr Opin Genet Dev. 2019 Mar 4;54:7-11. doi: 10.1016/j.gde.2019.02.003
Commun Biol. 2019 Feb 25;2:78. doi: 10.1038/s42003-019-0305-x. eCollection 2019.
Ann Surg Oncol. 2019 Jan;26(1):139-147. doi: 10.1245/s10434-018-7008-2. Epub 2018 Nov 9.
Nature 561, S48-S49 (2018); doi: 10.1038/d41586-018-06708-3
Human Molecular Genetics, Volume 27, Issue R2, 01 August 2018, Pages R99–R107
Nature Reviews Cancervolume 18, pages407–418 (2018)
Subscribe to our newsletter
Stay up-to-date on the latest advancements in 3D cell culture technology