Development of 3D Model of Intestinal Epithelium to Study Intestinal Stem Cell Fate and Proliferation
justine creff,
PhD Student,
LAAS
In tissues, cellular behavior is influenced by the three-dimensional microenvironment and involves a dynamic interplay between biochemical and mechanical signals. At the present time, most in vitro studies are restricted to two-dimension culture systems, which do not match the physiological growth conditions of cells. The development of 3D culture such as organoids has already shown their relevance, but these models fail to fully recapitulate the specificity and complexity of 3D microenvironment in vivo.
In this context, a new 3D model is being developed using photopolymerizable hydrogels to recapitulate more faithfully the architecture of the intestinal epithelium in vitro. A new biomaterial has been optimized, based on a PEG-DA (PolyEthylene Glycol DiAcrylate)/acrylic acid mix that can be supplemented with biological matrices such as collagen, fibronectin or laminin. These hydrogels were processed by 3D printing using a high-resolution stereolithography approach to create artificial 3D scaffolds matching the dimensions of mouse intestinal crypts and villi. This system has been validated with colorectal cancer cells and will be further optimized with sorted intestinal stem cells.
These intestinal scaffolds may constitute a complementary approach to organoid cultures to in vitro study ISCs and their progenies, as well as for in vitro drug screening and testing.
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