Proteomics of adipose derived cells and secretions: implications for renal failure

Adipose tissue is now viewed as an important endocrine organ through the actions of adipokines; and a source of multipotent adult mesenchymal stem cells termed adipose derived stem cells, or ADSCs. Adipokines, the term used for the protein secretions from adipose tissue, have been shown to have broad ranging effects on the body and have been shown to be involved in the pathogenesis or amelioration of disease processes. The paracrine effects of secretions from ADSCs have been shown to be the major driving force behind the therapeutic benefits of ADSC treatments in most cases. The work described here utilised protein secretion preparations derived from rodent and human adipose tissue produced in vitro to assess the potential of a secretion mixture as a therapeutic agent for renal disease. Renal disease is a growing problem world-wide with relatively little improvement in treatment regimens or drug effectiveness in the past twenty years. This thesis combines knowledge from the growing field of adipose cell-derived regenerative medicine and novel xenogeneic applications of proteomic techniques to test the effects of adipose tissue secretions on renal cells. Xenogeneic cell-based assays were developed to test the effects of the human adipose secretions on rodent primary renal cells (PRCs) and Madin-Darby canine kidney cells (MDCK cells). Novel applications of multiplexed cytokine assays were combined with quantitative proteomic analysis in order to gain a complex and meaningful understanding of the effects of the secretions on primary and immortalised renal cells. Simultaneous analysis of the secretory response to treatment by the PRCs and the uptake of human adipose secretions by the cells were performed, providing novel data on biological effects of the adipose secretions and the relevance of certain cytokines within the preparation. Proteomic analysis indicate broad suppression of TGF-β signalling pathways, increased resistance to apoptosis, altered cytoskeletal organisation and increased mitotic potential in the treated renal cell populations; effects that appear beneficial to the recovery from renal disease processes.