|Program and Abstracts
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Effects of Obesity and Diabetes Mellitus on Adipose Tissue Derived Stromal Cells- Implications for Health, Massive Weight Loss and Therapeutics.
Michael W. Findlay, MBBS, PhD, FRACS, FACS, Robert C. Rennert, MD, Michael Sorkin, MD, Michael Januszyk, MD, Peter A. Than, MD, Christopher Davis, MBBCh, MRCS, H. Peter Lorenz, MD, FACS, Homero Rivas, MD, MBA, FACS, John M. Morton, MD, FACS, Geoffrey C. Gurtner, MD, FACS.
Stanford University, Stanford, CA, USA.
The stromal vascular fraction of adipose tissue is a rich source of mesenchymal stem cells capable of tissue regeneration, immunomodulation and support of neovascularization. However, the results from adipose-derived stromal cell-based therapies are highly variable and our understanding of the role of these cells in normal health and their adaptations in disease are still evolving. Using single-cell microfluidics we sought to resolve the important subpopulations within the stromal vascular fraction. We then examined for variations in subpopulations between individuals in normal health and in the presence of common disease states such as obesity and diabetes mellitus.
Human adipose tissue samples harvested at the time of elective laparoscopic and esthetic surgeries and those derived from animal models were studied in parallel under appropriate Institutional Ethics and patient consent. Following cell isolation, the stromal vascular fraction (SVF) was enriched by lineage depletion using Magnetic Assisted Cell Sorting (MACS) before being sorted by Fluorescence-Activated Cell Sorting (FACS) using CD45, CD31 and CD34 labeled fluorophores. The gene expression profiles of individual cells were then examined by studying 96 genes across a spectrum of stemness, surface marker, neovascularization, replication, differentiation and common second messenger pathways. A cluster-based algorithm using fuzzy-C means was then applied to resolve the important subpopulations within the SVF. Patient health information and animal models of diet-induced obesity and diabetes mellitus were used to stratify subpopulation profiles by health status with correlation to important clinical outcomes such as post-operative complications and ischemic events.
A total of 68 patients were studied including 32 obese, 5 diabetic, 12 obese and diabetic and 19 control patients. A minimum of 6 animals per group were also studied. A specific subpopulation of stem cells within the adipose SVF was consistently depleted in morbidly obese and diabetic individuals with up to a nine-fold reduction in this subpopulation when compared with healthy controls (p<0.0065). This subpopulation depletion was present in both humans and animal models of obesity and/or diabetes mellitus and was maintained on dual and multi-channel clustering, indicating the significance of the subpopulation. In-vitro studies demonstrated the stemness of this mesenchymal population with multi-lineage potential and the gene expression profile of these cells indicating putative roles in neovascularization and tissue regeneration.
A novel stem cell subpopulation depletion has been identified in patients with obesity and/or diabetes mellitus with important implications for our understanding of the complication profiles of these conditions and for the development of targeted cell-based and molecular therapies to address issues such as wound healing and regeneration following ischemia.
Figure 1- SVF subpopulation depletion in obese individuals (red column) when compared with non-obese controls (blue), (p=0.0065, two-tailed t-test).
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