Accueil du site > Equipes > Biologie et Ingénierie du Cartilage (F. Mallein-Gerin) > Thématiques > Influence de l’architecture tridimensionnelle et de divers biomatériaux sur le phénotype des chondrocytes > Influence de l’architecture tridimensionnelle et de divers biomatériaux sur le phénotype des chondrocytes
Project leader : E. Perrier-Groult
People involved in the project : Marielle Pasdeloup
Influence of 3D environment and biomaterials on the chondrocyte phenotype
The cell shape and more exactly the actin cytoskeleton controls the status of the chondrocyte phenotype. The expansion of chondrocytes in 2D cell culture conditions is capable of providing a large number of cells. The passaged chondrocytes are large, spread, and have actin organized into stress fibers. This cell morphology and cytoskeletal organization correspond in fact to a dedifferentiated state of the chondrocytes which no longer synthesize cartilage matrix proteins. This is in contrast to small, round primary chondrocytes which show cortical distribution of actin in native cartilage. Interestingly, embedding of chondrocytes in a 3D environment provokes actin depolymerization and cortical rearrangement. In this situation, the chondrocytes can re-express a differentiated phenotype. Polymerization of actin is regulated by the GTPase RhoA and the amount and activity of RhoA is dramatically downregulated when chondrocytes are embedded in 3D environment.
Therefore, 3D cell model systems combining chondrocytes and biomaterials like hydrogels support proper chondrogenesis and good cartilage matrix production. We use such 3D matrices to study the molecular mechanisms of chondrogenesis and to develop innovative tissue engineering protocols for cartilage repair (figure 1).
Figure 1 : Human chondrocytes were expanded on plastic then allowd to redifferentiate in hydrogel. This histological section of the hydrogel was immunolabeled with an antibody against type II collagen, the major protein of cartilage. Of note, three cells share their extracellular matrix that was newly-synthesized in the hydrogel, a good sign of tissue formation.
1- Perrier-Groult E, Pasdeloup M, Malbouyres M, Galéra P, Mallein-Gerin F. (2013) Control of collagen production in mouse chondrocytes by using a combination of bone morphogenetic protein-2 and small interfering RNA targeting col1a1 for hydrogel-based tissue-engineered cartilage. Tissue Eng. Part C. 19 : 652-664.
2- Durbec M, Mayer N, Vertu-Ciolino D, Disant F, Mallein-Gerin F, Perrier-Groult E. (2014) Reconstruction of cartilage nasal defects using a tissue engineering technique based on combination of high-density polyethylene and hydrogel. Pathol. Biol. 62 : 137-145.
Pr. O. Damour, Laboratory of cutaneus substitutes and bank of tissue and cells, Hôpital Edouard Herriot, Lyon, France
Pr. F. Disant, Ear Nose and Throat service and oral maxillofacial surgery , Hôpital Edouard Herriot, Lyon, France