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

Abstract

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

Alterations in the Secretome of Clinically Relevant Preparations of Adipose-Derived Mesenchymal Stem Cells Cocultured with Hyaluronan

“…However, differentiation is not the primary mode of action and in vitro animal models and human data have demonstrated that a complex set of secretions drive the anti-inflammatory and regenerative effects that have been observed [ 29 ]. Thus, the secretome of MSCs has become of particular interest and multiplex cytokine analyses are used to assess cell populations and the “cytokine profile” is predictive of in vivo effect [ 30 ]. Proinflammatory cytokines such as Interleukin-1 β (IL-1 β ) play a pivotal role in the pathogenesis of OA.…”