Therapy free of cells vs human mesenchymal stem cells from umbilical cord stroma to treat the inflammation in OA

M Morente-López(1,2,3) R Mato-Basalo(1,2,3) S Lucio-Gallego(1,2,3) L Silva(2) A García-Sanchéz(2) J De Toro(1,2) J A Fafián-Labora(1,2,3) M C Arufe(1,2,3)

1:Universidade da Coruña; 2:INIBIC; 3:CICA

In the last decade, extracellular vesicles in combination with the use of miRNAs to modify post-transcriptional expressions of multiple genes have shown their utility in new therapies to treat inflammatory diseases. This work delves into the anti-inflammatory effect of extracellular vesicles derived from mesenchymal stem cells previously modified so that the expression of miR-21 is inhibited. We compare the efficacy of two treatments, mesenchymal stem cell with their miR-21 inhibited through lentiviral transfection and their derived extracellular vesicles, against inflammation in a new OA animal model. The modified mesenchymal stem cell and their extracellular vesicles were intraperitoneally injected  in an OA animal model by twice. One month after treatment, the animals were eutanized to check which therapy was the most affective to reduce inflammation compares with animals untreated. Treated OA model sera were analyzed for cytokines and chemokines. Subsequently, different organs were analyzed to validate the results obtained. Extracellular vesicles were the most efective treatment to reduce SASP as well as chemocines and cytokines in serum of OA animals compared with mesenchymal stem cells alone in a statistically significant way. Besides, miR-21 is acting through ERK1/2 pathway which is envolved into inflammation. Syndecan 1 seems to be involved into this communication between SASP and inflammation as well as extracelular vesicles production,  which make it a good candidate to generate a new anti-inflammatory therapy.