Mesenchymal stem cells-derived micropellet is a relevant in vitro model for biomechanical modeling of cartilage growth

Gilles Dusfour (1, 2) , Marie Maumus (3) , Simon Le Floc'H (1, 2) , Dominique Ambard (1, 2) , Christian Jorgensen (3) , Danièle Noel (3) , Patrick Cañadas (1, 2)

1 LMGC - Laboratoire de Mécanique et Génie Civil
2 BIOTIC - Biomécanique des Interactions et de l'Organisation des Tissus et des Cellules
3 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)

Articular cartilage is a connective tissue, composed of chondrocytes, which represent a small volumetric fraction of about 2%, and an extracellular matrix, rich in collagens and proteoglycans [1]. The main biological function of articular cartilage is to permit frictionless movements of the connected bones while facilitating force transmission. Cartilage therefore exhibits a sufficient rigidity to resist mechanical loading and absorbs a part of the contact energy between the related bones. However, articular cartilage is a non-vascularized tissue with limited self-healing and repair capacities. With aging and disease, articular cartilage fails to respond to biomechanical stimuli resulting in impaired capacity of regeneration. Better understanding the processes of mechanotransduction and cartilage growth will speed up the improvement of tissue engineering approaches In the present study, we used the in vitro model of cartilage micropellets obtained from the differentiation of mesenchymal stem cells (MSC) into chondrocytes by 3D-culture in presence of TGFβ3 inducing factor [2]. These cartilage micropellets were submitted to mechanical loading (i.e., compression tests by using a home-made compression device) and biochemical analysis (i.e., RTqPCR and immunocytochemistry) after respectively 7, 14, 21, 29 and 35 days of cell differentiation. This cross analysis showed that generated micropellets exhibit properties which are close to those of human native articular cartilage in terms of mechanical properties and gene expression. In particular, the elasticity modulus falls into the range of values obtained by using AFM on nondegraded articular cartilage at nanometer scale (i.e., actually 150 kPa vs 83 kPa in [3]). Moreover, temporal evolution of the mechanical properties was correlated with gene expression levels of type II collagen and LINK protein. The present results confirm that MSC-derived cartilage micropellets are relevant in vitro models devoted to mechanobiological and biomechanical studies of cartilage growth.

Domaines: Biomécanique [physics.med-ph]

Gilles Dusfour, Marie Maumus, Simon Le Floc'H, Dominique Ambard, Christian Jorgensen, et al.. Mesenchymal stem cells-derived micropellet is a relevant in vitro model for biomechanical modeling of cartilage growth. 8th World Congress of Biomechanics, Jul 2018, Dublin, Ireland. ⟨hal-01767884⟩