Defined three-dimensional microenvironments boost induction of pluripotency

Massimiliano Caiazzo, Yuya Okawa, Adrian Ranga, Alessandra Piersigilli, Yoji Tabata, Matthias P Lutolf

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)344-52
Number of pages9
JournalNature Materials
Volume15
Issue number3
DOIs
Publication statusPublished - 11 Jan 2016

Keywords

  • Animals
  • Cell Culture Techniques
  • Cell Differentiation
  • Cellular Microenvironment
  • Epithelial Cells
  • Gene Expression Regulation
  • Humans
  • Materials Testing
  • Mesenchymal Stromal Cells
  • Mice
  • Pluripotent Stem Cells
  • Journal Article
  • Research Support, Non-U.S. Gov't

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