Plastic Surgery Research Council
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PSRC 60th Annual Meeting
Program and Abstracts

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Impaired Regenerative Ability of Aged and Diabetic Adipose Derived Stem Cells is Caused by Depletion of Cell Subpopulations
Dominik Duscher, MD1; Robert. C. Rennert, MD1; Michael Januszyk, MD1; Zeshaan N. Maan, MD1; Alexander J. Whittam, BA1; Graham G. Walmsley, BA1,2; Michael S. Hu, MD1; Geoffrey C. Gurtner, MD1
1Stanford University, Division of Plastic Surgery, Stanford, CA, 2Stanford University, Institute for Stem Cell Biology and Regenerative Medicine, Stanford

Introduction: Neovascularization is essential for tissue repair. Both aged and diabetic patients suffer from a reduced neovascular response leading to complications in wound healing. While it has been shown that mesenchymal stem cells derived from adipose tissue (ASCs) promote tissue regeneration, it also becomes increasingly clear that their function is impaired in aged and diabetic populations. Here we investigate the impact of aging and diabetes on the regenerative potential of ASCs.
Material and Methods: ASCs were harvested from young, diabetic and aged mice and their viability, proliferation, neovasculogenic capacity and regenerative cytokine profile were compared. Furthermore, their effect on wound healing was determined and microfluidic single-cell gene expression analysis was performed.
Results: Aged and diabetic ASCs are compromised in their ability to establish a vascular network both in vitro and in vivo (*p<0.05). This is likely due to reduced expression of pro-angiogenic and anti-oxidative cytokines (Angpt-1, VEGFa, HGF, SOD3 and SOD2; *p<0.05). Seeding onto a regenerative biomimetic hydrogel fails to rescue the functional impairment of aged and diabetic ASCs resulting in delayed wound healing (*p<0.05) and reduced wound-vascularity upon healing (*p<0.05). Utilizing single cell transcriptional analysis to examine the composition of the ASC population, we identified a subpopulation of cells defined by the expression of genes associated with stemness, tissue remodeling and vasculogenesis, which was diminished in aged and diabetic mice.
Conclusion: Our results implicate a novel pathophysiologic mechanism underlying ASC dysfunction in aged and diabetic populations and that the utility of autologous ASCs for cell-based therapies in these patients may be limited.


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