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Design of a nanocomposite substrate inducing adult stem cell assembly and progression toward an Epiblast-like or primitive endoderm-like phenotype via mechanotransduction

Morena, Francesco, Armentano, Ilaria, Montanucci, Pia, Argentati, Chiara, Fortunati, Elena, Montesano, Simona, Bicchi, Ilaria, Pescara, Teresa, Pennoni, Ilaria, Mattioli, Samantha, Torre, Luigi, Latterini, Loredana, Emiliani, Carla, Basta, Giuseppe, Calafiore, Riccardo, Kenny, Josè Maria, Martino, Sabata
Biomaterials 2017
GATA transcription factors, actin, adherens junctions, adult stem cells, carbon nanotubes, chromatin, humans, mechanotransduction, models, nanocomposites, phenotype, steers, transcription (genetics), umbilical cord
This work shows that the active interaction between human umbilical cord matrix stem cells and Poly (l-lactide)acid (PLLA) and PLLA/Multi Walled Carbon Nanotubes (MWCNTs) nanocomposite films results in the stem cell assembly as a spheroid conformation and affects the stem cell fate transition.We demonstrated that spheroids directly respond to a tunable surface and the bulk properties (electric, dielectric and thermal) of plain and nanocomposite PLLA films by triggering a mechanotransduction axis. This stepwise process starts from tethering of the cells' focal adhesion proteins to the surface, together with the adherens junctions between cells. Both complexes transmit traction forces to F-Actin stress fibres that link Filamin-A and Myosin-IIA proteins, generating a biological scaffold, with increased stiffening conformation from PLLA to PLLA/MWCNTs, and enable the nucleoskeleton proteins to boost chromatin reprogramming processes. Herein, the opposite expression of NANOG and GATA6 transcription factors, together with other lineage specification related proteins, steer spheroids toward an Epiblast-like or Primitive-Endoderm-like lineage commitment, depending on the absence or presence of 1 wt% MWCNTs, respectively.This work represents a pioneering effort to create a stem cell/material interface that can model the stem cell fate transition under growth culture conditions.