M. W. Findlay1,2, M. Sorkin1, R. Rennert1, M. Januszyk1, P. Than1, M. Rodrigues1, Z. Maan1, A. Whittam1, D. Duscher1, H. Rivas1, H. P. Lorenz1, J. M. Morton1, G. Gurtner1 1Stanford University,Department Of Surgery,Palo Alto, CA, USA 2University Of Melbourne,Department Of Surgery Royal Melbourne Hospital,Parkville, VIC, Australia
Introduction: Adipose tissue is a rich source of human stem cells (hASC’s) that can support fundamental tissue processes such as neovascularization, tissue regeneration and immune modulation. Despite increases in obesity, bariatric surgery and post-bariatric plastic surgery in developed countries, little is known about the impact of morbid obesity on adipose-derived stem cell populations and stem cell-mediated health. Bariatric surgery helps reduce obesity-related morbidity and mortality through multimodal effects on blood pressure, blood lipids and glucose homeostasis, but despite this, the risk profile for post-bariatric patients does not return to normal. We examined stem cell populations in bariatric patients to determine whether morbid obesity could adversely impact hASC’s and stem-cell related health.
Methods: Under appropriate Institutional Ethics and patient consent, human adipose tissue samples were harvested during elective laparoscopic and aesthetic surgeries at Stanford University Medical Centre. The stromal vascular fraction (SVF) was isolated, lineage depleted by Magnetic Assisted Cell Sorting (MACS) before the resulting cell suspension was sorted by Fluorescence-Activated Cell Sorting (FACS) using CD45, CD31 and CD34 labeled fluorophores. A single-cell microfluidics approach was then applied to quantify gene expression in 96 genes across a spectrum of stemness, surface marker, neovascularization, replication, differentiation and common second messenger pathways. An algorithm was then applied to assess for clustering into specific subpopulations of stem cells with correlation between the groups. Murine studies were undertaken in parallel to examine potential mechanisms for any effect.
Results:15 bariatric patients and 5 controls were enrolled in the study. A nine-fold reduction in a specific subpopulation of mesenchymal stromal cells was identified in bariatric patients when compared with non-obese controls (See Figure). This deficient subpopulation was maintained on dual and multi-channel clustering, indicating the significance of the subpopulation. Murine studies demonstrated a linkage with diabetes mellitus by displaying the same subpopulation deficiency in streptozotocin-induced diabetic animals.
Conclusion:The clinical profile of morbid obesity is more complex than its effects on blood glucose, lipids and blood pressure. We have demonstrated a specific subpopulation of stem cells that it deficient in obese individuals with potential relevance for stem cell-mediated processes such as wound healing, tissue repair and regeneration after ischemia.
