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