Treatment of a mouse model of collagen antibody-induced arthritis with human adipose-derived secretions

Abstract

The use of\radipose-derived cells as a treatment for a variety of diseases is becoming\rincreasingly common. These therapies include the use of cultured mesenchymal stem\rcells (MSCs) and freshly isolated stromal vascular fraction (SVF) alone, or in\rconjunction with other cells such as adipocytes. There is a substantial amount\rof literature published on the therapeutic properties of MSCs and their\rsecretions as the main driver of their therapeutic effect. However, there is\rlittle data available on the therapeutic potential of secretions from SVF,\reither with or without adipocytes. We investigated the ability of secretions\rfrom human adipose SVF alone and the SVF co-cultured with adipocytes as a proxy\rfor cell therapy, to ameliorate an inflammatory disorder. This ethics approved\rstudy involved the treatment of collagen antibody-induced arthritis (CAIA) in\rmice with secretions from SVF, SVF co-cultured with adipocytes, or a vehicle\rcontrol via both intravenous (IV) and intramuscular (IM) routes. Treatment\routcome was assessed by paw volume, ankle size and clinical arthritis score\rmeasurements. Serum samples were obtained following euthanasia and analysed for\ra panel of 32 mouse cytokines and growth factors. The dose and timing regime\rused for the IM administration of both human secretion mixtures did not\rsignificantly ameliorate arthritis in this model. The IV administration of SVF\radipocyte co-culture secretions reduced the paw volume, and significantly\rreduced the ankle size and clinical arthritis score when compared to the IV vehicle\rcontrol mice. This was a superior therapeutic effect than treatment with SVF\rsecretions. Furthermore, treatment with SVF adipocyte coculture secretions\rresulted in a significant reduction in serum levels of key cytokines, IL-2 and\rVEGF, involved in the pathogenesis of rheumatoid arthritis. Therefore, the SVF cocultured\rwith adipocytes is an attractive therapeutic for inflammatory conditions.