To add the extracellular matrix in your 3D cellular assays

Context

It is well established that the extracellular matrix (ECM) plays a central role in cell homeostasis and cell adhesion by providing support, promoting cell-to-cell communication and differentiation (or dedifferentiation and tumoral progression when the ECM is modified). The composition but also the stiffness and elasticity of the ECM have important implications in cell migration, gene expression and differentiation. Components of the ECM are produced intracellularly by resident cells and secreted into the ECM via exocytosis. The ECM includes the interstitial matrix and the basement membrane. The ECM is formed by gels of polysaccharides and fibrous proteins.

Hyaluronic Acid (HA) is an essential component of the ECM. It is a polysaccharide consisting of alternating residues of D-glucuronic acid and N-acetylglucosamine, and unlike other glycosaminoglycans (GAGs), is not found as a proteoglycan. HA in the extracellular space confers to tissues the ability to resist compression by providing a counteracting turgor force and  absorbing significant amounts of water. Hyaluronic acid is thus found in abundance in the ECM of load-bearing joints for example. It is also a chief component of the interstitial gel. HA acts as an environmental cue that regulates cell behavior during embryonic development, healing processes, inflammation, and tumor development. It interacts with a transmembrane receptor, CD44.

To mimic the ECM, we Need to know the physicochemical properties (mechanical & composition) in normal and pathological organs :

  • mechanical properties : elastic modulus of organs’ ECM

  • composition of ECM : During different pathologies (like liver fibrosis or cancer), the secretion of collagen and GAGs is modified, therefore modifying the stiffness of the environment

Ex : Modification of the ECM of the liver during the different steps of liver disease : steatosis, NASH, fibrosis, cirrhosis

Ex : Disruption of ECM during tumor progression

=> BIOMIMESYS® 3D technology (patented)

For each organ (healthy or pathologic), we can develop a specific hydroscaffold ECM, by fine tuning its elastic modulus and its composition.