Introduction - Rheumatoid arthritis (RA) is an inflammatory disease of which there is no cure. Cell therapies using umbilical cord mesenchymal stromal cells (UC-MSCs) are becoming a popular possibility for treatment due to their ability to promote immunosuppression. Extracellular vesicles (EVs) mimic this but offer the advantage of safety (no malignant transformation or rejection), being easily stored and an extended shelf life. Hence, we sought to determine the ability of UC-MSCs, and their derived EVs, to treat RA using an antigen induced model of arthritis (AIA).
Methods - Mice were injected with 5x105 UC-MSCs, or equivalent EVs from the same cell number, 24 hours post-arthritis induction. Cells were characterised by flow cytometry and EVs by Tunable Resistive Pulse Sensing (IZON) and cryo-electron microscopy following isolation using ultracentrifugation with a 30% sucrose cushion. Joint swelling was assessed over 72 hours, after which histological analysis was performed.
Results - Cells displayed the expected phenotype markers for MSCs. EVs from 5x105 cells yielded 2.15x109 particles/ml with a mean size of 166±70nm, of which most particles displayed an EV-like morphology of a double lipid membrane bilayer. Joint swelling decreased for both treatments, in comparison to control, but only MSC-EV treated mice achieved significance (P< 0.01) at the 72-hour timepoint. EV superiority over UC-MSCs was reflected in the histological scoring, with EVs achieving a consistently lower mean score in comparison to controls (improved clinical outcome), whilst cells showed higher mean scores (worse clinical outcome).
Summary and Conclusion - In this study, EVs appear to be superior to their cell counterparts when treating an arthritis model. This supports the argument that MSC-EVs may be a suitable therapy to treat RA.
Funding - EPSRC/MRC DTC in Regenerative Medicine, The James Richardson Studentship, Institute of Orthopaedics Ltd., Oswestry and ACORN funding, Keele University.