Mesenchymal Stem Cells-derived cartilage micropellet: a relevant model for biomechanical and mechanobiological modelisation of cartilage growth

Abstract : 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.
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Submitted on : Tuesday, April 17, 2018 - 2:10:01 PM
Last modification on : Thursday, March 7, 2019 - 10:14:02 AM

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Marie Maumus, Gilles Dusfour, Simon Le Floc'H, Dominique Ambard, Christian Jorgensen, et al.. Mesenchymal Stem Cells-derived cartilage micropellet: a relevant model for biomechanical and mechanobiological modelisation of cartilage growth. 2018 eCM XVIII: Cartilage & Disc: Repair and Regeneration, Jun 2018, Davos, Switzerland. ⟨hal-01768746⟩

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