Mesenchymal Stem Cells-derived cartilage micropellet: a relevant model for biomechanical and mechanobiological modelisation of cartilage growth
Résumé
INTRODUCTION: Articular cartilage is a connective tissue, composed of chondrocytes 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. The aim of this study is to set up a
compression device to measure biomechanical properties of cartilage micropellets in different conditions to
have a modelisation of cartilage growth.
METHODS: In the present study, we used the in vitro model of cartilage micropellets obtained from the
differentiation of human mesenchymal stem cells (MSC) into chondrocytes by 3D-culture in presence of the
inducing factor TGFβ3 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., RT-qPCR and
immunocytochemistry) after respectively 7, 14, 21, 29 and 35 days of cell differentiation.
RESULTS: This cross analysis showed that micropellets generated with TGFβ3 exhibit a significant higher
Young’s modulus and disspated energy than undifferentiated micropellets (generated without TGFβ3). These
data reflected the visco-elastic mechanical properties of micropellets that are close to those of human native
articular cartilage. In particular, the elasticity modulus felt into the range of values obtained by using AFM on
non-degraded articular cartilage at nanometer scale (i.e., actually 150 kPa vs 83 kPa3). Interestingly, we could
not measure the mechanical properties of micropellets during the two first weeks of culture where production
of the cartilage matrix components was low. The Young’s modulus and the dissipated energy both increased
from day 14 to day 29 in parallel to the increase of chondrocyte gene expression. Finally, the mechanical
properties were highly correlated with gene expression levels of type II collagen and LINK protein.
DISCUSSION & CONCLUSIONS: The present results confirm that MSC-derived cartilage micropellets
are a relevant in vitro model devoted to mechanobiological and biomechanical studies of cartilage growth.