Investigation of the properties of adipose-derived cells and secretions

Adipose tissue is no longer considered to be a simple energy storage organ but is now recognized as an endocrine organ which plays a role in a number of bodily processes. Adipose tissue is also a rich source of mesenchymal stem cells (MSCs), which has made it an attractive tissue for adult cell therapy. Relatively large quantities can be obtained at very low risk, discomfort or inconvenience to the patient using routine liposuction and it can be processed rapidly with minimal manipulation and re-administered to the patients area of need. Consequently, cultured MSCs and uncultured adipose-derived stromal vascular fraction cells (SVF) alone, or combined with other cells such as adipocytes, are being offered commercially for the treatment of a variety of diseases. Whilst a significant amount of research has been performed and published on MSCs, many of these studies have focused on the ability to differentiate these cells into a target cell type and their subsequent therapeutic use in this differentiated state. However, secretions are now considered to be a major driver of the therapeutic effect of cell therapy and therefore in vitro assessments of differentiation potential are not an appropriate measure of in vivo efficacy of the cells. This thesis focused on investigating the in vitro secretion capabilities of different adipose-derived cell populations and their subsequent in vivo use. Using a multiplex cytokine analysis approach, this work demonstrated that the entire cellular composition of adipose tissue (the SVF with adipocytes) produces a distinct secretion profile in vitro when compared to the secretion profiles from isolated cell populations. The administration of these secretions from different adipose-derived cell populations to a collagen antibody-induced arthritis model in mice confirmed the in vitro secretion profile results. These results indicated that the use of the entire cellular composition of adipose tissue, the SVF with adipocytes, is a viable therapeutic. Additionally, the adipose-derived cell populations were exposed to a limited number of environmental conditions in vitro to investigate whether a targeted set of secretions could be produced for the treatment of a particular disease. These results indicated that secretion profiles of adipose-derived cell populations could be modulated by different environmental conditions and consequently, the use of secretions as an adjunct or subsequent booster after cellular therapy may be an attractive option for the treatment of inflammatory diseases and degenerative conditions. The work presented in this thesis also demonstrated that a multiplex cytokine analysis approach can be used as a measure of the secretion capabilities of cells in vitro, a predictor of in vivo efficacy and as an objective biological metric of the treatment effect in vivo.