Extracellular vesicles for osteoarthritis therapy

As a result of the aging population, osteoarthritis (OA) is becoming the fifteenth-highest leading cause of disability affecting over 7% of the global population. OA is hallmarked by the degradation of cartilage which covers the bony ends leading to pain and impairment of movement of affected patients. The number of diseased people aged 60 years old and above is predicted to double by 2050 and more than triple by 2100. OA not only is a disease affecting joints but also has a major impact on social life of patients as social isolation, depression, and involuntary unemployment due to disability make OA also a socioeconomic burden. Till now, treatment options for OA are mainly palliative focusing on relieve of pain and inflammation, but do not result in a fully restoration of the joints mechanical function. Over a decade, cell-based therapies have been a useful tool to treat cartilage defects. Besides chondrocytes, which are the only cell type within cartilage, application of stem cells led to promising outcomes. Stem cells possess the capability to differentiate into any kind of cell (e.g., muscle cell, bone cell, nerve cell among others) in order to replace the damaged tissue. But it has been shown that not only the differentiation of the stem cell contributes to improvement but also the secretion of nano-sized soluble factors, especially extracellular vesicles (EVs), mediate regeneration of cartilage. As a response to external stimuli (e.g., inflammatory signals, food deprivation) cells can communicate with each other by releasing EVs containing various signals in form of bioactive molecules (e.g., miRNAs, proteins). These EVs are then taken up by a neighbor cell liberating their content which then leads to a respective cellular answer according to the content of the EVs. The aim of this project is to determine how various external stimuli influence the therapeutic effect of EVs isolated from adipose derives stem cells. Therefore, stem cells will be treated with different stimuli (inflammation, low oxygen availability, pro-chondrogenic signals) before EVs will be isolated. Chondrocytes derived from osteoarthritic patients will be treated with these primed EVs and it will be determined which cellular pre-treatment elicits the highest regenerative effect. Furthermore, a defect will be created in a cartilage piece and EVs from the respective treatments will be inserted within this defect. The repair capacity will be evaluated by various assays. If healing of cartilage could be achieved in this ex vivo model, translation of this approach could give back quality of life to millions of patients suffering from OA.

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