Stem Cell Reviews and Reports

, Volume 15, Issue 1, pp 82–92 | Cite as

Use of a PTFE Micro-Bioreactor to Promote 3D Cell Rearrangement and Maintain High Plasticity in Epigenetically Erased Fibroblasts

  • Georgia Pennarossa
  • Elena F. M. Manzoni
  • Sergio Ledda
  • Magda deEguileor
  • Fulvio Gandolfi
  • Tiziana A. L. BreviniEmail author


Phenotype definition is driven by epigenetic mechanisms as well as directly influenced by the cell microenvironment and by biophysical signals deriving from the extracellular matrix. The possibility to interact with the epigenetic signature of an adult mature cell, reversing its differentiated state and inducing a short transient high plasticity window, was previously demonstrated. In parallel, in vitro studies have shown that 3D culture systems, mimicking cell native tissue, exert significant effects on cell behavior and functions. Here we report the production of “PTFE micro-bioreactors” for long-term culture of epigenetically derived high plasticity cells. The system promotes 3D cell rearrangement, global DNA demethylation and elevated transcription of pluripotency markers, that is dependent on WW domain containing transcription regulator 1 (TAZ) nuclear accumulation and SMAD family member 2 (SMAD2) co-shuttling. Our findings demonstrate that the use of 3D culture strategies greatly improves the induction and maintenance of a high plasticity state.


Epigenetic erasing High plasticity Micro-bioreactor PTFE SMAD2 TAZ 



This work was funded by Carraresi Foundation. The Laboratory of Biomedical Embryology is member of the COST Action CA16119 In vitro 3-D total cell guidance and fitness (CellFit), and the COST Action CM1406 Epigenetic Chemical Biology (EPICHEM). We thank Prof. E. Somigliana for kindly providing human skin biopsies.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Georgia Pennarossa
    • 1
  • Elena F. M. Manzoni
    • 1
  • Sergio Ledda
    • 2
  • Magda deEguileor
    • 3
  • Fulvio Gandolfi
    • 4
    • 5
  • Tiziana A. L. Brevini
    • 1
    • 5
    Email author
  1. 1.Laboratory of Biomedical Embryology, Department of Health, Animal Science and Food SafetyUniversità degli Studi di MilanoMilanItaly
  2. 2.Department of Veterinary MedicineUniversity of SassariSassariItaly
  3. 3.Department of Biotechnology and Life SciencesUniversità degli Studi dell’InsubriaVareseItaly
  4. 4.Laboratory of Biomedical Embryology, Department of Agricultural and Environmental Sciences - Production, Landscape, AgroenergyUniversity of MilanMilanItaly
  5. 5.Unistem, Centre for Stem Cell ResearchUniversita’ degli Studi di MilanoMilanItaly

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