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Artificial Niche Microarray; a Multifactorial Approach for Deciphering Cell-Microenvironment Interactions

le 18 janvier 2017
à 11h

Samy Gobaa, Institut Pasteur, Center forInnovation and Technological Research, Biomaterials and Microfluidics platform,Paris, France

Understanding the regulatory role of the multi-factorial niche in directing single stem cell fate calls for sophisticated in vitro models. Ideally, artificial platforms that aim at recapitulating such complexity should allow interrogating biochemical and biophysical niche effectors in combinatorial fashion and in the context of a physiologically relevant cell culture substrate. In order to meet these requirements, we engineered a cell culture platform consisting of soft hydrogel microwell arrays with modular stiffness (between ca. 4-20kPa), wherein individual microwells are functionalized with combinatorial protein mixtures spotted by robotic technology. This artificial niche microarray platform enables the study of self-renewal and differentiation of both adherent and non-adherent stem cells. In order to take advantage of the high throughput capabilities of this platform we also produced a, custom-made, high content image analysis pipeline. We have applied the system to investigate 1-the effect of immobilized proteins combinations and 2-the rigidity of the substrate on mesenchymal stem cell differentiation. We demonstrated that cell-cell interactions can be partially recapitulated by the display of biomolecules. In a second step, we employed a 3D version of the artificial niche array platform to dissect the microenvironment cues that underlie pluripotency maintenance in ES cells. These experiments demonstrated that the artificial niche array toolset is a simple yet versatile platform capable of deconstructing the complexity of multifactorial microenvironments.

Lieu(x) :
Auditorium Daniel Chemla, Bâtiment IDA

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