Chondrogenesis-inductive Systems Comprising Extracellular Vesicles Derived from Chondrocytic Cells

Articular cartilage is a connective tissue with low self-regeneration potential due to its avascular nature and lack of access to progenitor cells. Therefore, cartilage regeneration is an unmet clinical need and then it is an important candidate for tissue engineering and regenerative medicine strategies. Extracellular vesicles (EVs) are lipidic particles secreted by cells to deliver biological signals, being increasingly studied biomarker due to its regenerative potential. Specifically, EVs derived from hBM-MSCs can be used for controlling inflammation, repairing injury and enhancing tissue regeneration ^{[1, 2]}.

This work aims to develop a system capable of selectively binding EVs present in conditioned medium obtained from human articular chondrocytes (hACs) or chondrogenically induced human bone marrow mesenchymal stem cells (hBMSC). For that, CD63 antibody was immobilized at the surface of an activated and functionalized electrospun nanofibrous substrate. The chondrogenic potential of bound EVs was further assessed by culturing hBM-MSCs over the substrates during 28 days under basal conditions. EVs-derived from hACs cultured under differentiation medium induced the expression of specific chondrogenic markers namely SOX9, COMP, Aggrecan, Collagen type II, as well as glycosaminoglycans synthesis. Both EVs system outperformed the currently used chondroinductive strategies. These data show that naturally secreted EVs can guide the chondrogenic commitment of hBMSCs in the absence of other chemical or genetic chondroinductors.

^[1] Bian, S. Y., et al., J Mol Med, 2014; ^[2] Martins, M., et al., Stem Cell Rep,2016;

Acknowledgements

The authors would like to acknowledge the Portuguese Foundation for Science and Technology (FCT) for the PhD grant of M.R.C. (PD/BD/113797/2015) financed by the FCT Doctoral Program on Advanced Therapies for Health (PATH) (FSE/POCH/PD/169/2013), the IF grant of A.M. (IF/00376/2014), and the projects SPARTAN (PTDC/CTM-BIO/4388/2014) and FRONthera (NORTE-01-0145-FEDER-0000232).