Fundamental Research Division
The DRF at the CEA assemble approximately 6,000 scientists since January 2016.
Découvertes et avancées | Scientific result | Pharmacology | Cellular mechanisms | Diagnosis and innovative treatment | Methodologies for life sciences
Using almost fully automated processes, researchers at Irig have designed a three-dimensional microenvironment in which cells form a tissue resembling a mini-tumor. Their work opens new perspectives for personalized medicine.
The study of cancer cells is constrained by the lack of diagnostic tools, as well as by the existing models.
Currently, tissue cultures on rigid supports (either plastic or glass) are unable to reproduce the biophysical, chemical and physiological conditions of a tumor microenvironment. In addition, current in vivo models require lengthy and costly procedures and raise ethical issues related to the manipulation of animals.
It is therefore of particular interest to develop new in vitro models that can mimic the tumor microenvironment in vivo, at all stages of development.
In vivo, a tumor is surrounded by an extracellular matrix. This matrix is a tangled network of proteins, sugars and growth factors. It provides cancer cells with the proteins necessary for their biochemical and structural support, as well as the growth factors that influence cellular responses. In addition, it allows them to communicate with each other through biochemical and mechanical signals.
Irig researchers are currently using multilayer polyelectrolyte films to mimic the composition of this matrix. This allows them to modulate the thickness, chemistry and mechanical properties of these biomimetic nanofilms, which can deliver proteins and drugs to human cells. These films can be deposited by an automated process on three-dimensional scaffolds by photopolymerization of a resin, making it possible to create 3D architectures with bio-functionalized surfaces.
Drawing on their previous work, they selected films based on hyaluronic acid – one of the main constituents of skin – and poly-L-lysine, a polypeptide commonly used in cell culture. After processing, these films are then chemically cross-linked to modulate their rigidity and, in a final step, proteins are loaded into the films.
As a result, the films possess two major characteristics of the extracellular matrix:
In this synthetic, bioactive microenvironment, the scientists have found that the cancer cells self-organize, migrate and proliferate to form a three-dimensional microtumor-like tissue. Pancreatic cancer cell adhesion and proliferation are influenced by biomechanical and biochemical signals from the biomimetic film in a cell type-specific manner. In particular, type 2 and 4 bone morphogenetic proteins appear to be important factors in pancreatic cancer.
Engineering of a microscale niche for pancreatic tumor cells using bioactive film coatings combined with 3D-architectured scaffolds, ACS Applied Materials & Interfaces
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.