Yu-Chung Shih 石育仲

  • Adipose-derived stem cells and stromal vascular fraction improve venous stenosis in mouse arteriovenous fistula

    Uremic patients rely on vascular access for hemodialysis, and vascular access dysfunction constitutes a major cause of morbidity in dialysis patients. Arteriovenous fistula (AVF) is the preferred vascular access due to lower complication rates, but the 1-year patency rate of AVF is still only about 60%. We use a mouse arterial-end-to-venous-side AVF model to simulate the flow pattern and AVF stenosis in patients. Neointima develops gradually in the venous outflow tract of AVF and reaches about 80% stenosis at 4 weeks after AVF creation. We applied uncultured cell mixture after collagenase decomposition of adipose tissue, stromal vascular fraction (SVF), and also cultured adipose derived stem cells (ASCs) directly around the AVF after its creation. AVFs treated by either SVF or ASCs showed increased lumen area and also reduced ratio of neointima to the internal elastic lamina area. Both treatments reduced α-SMA(+) cells in the neointima. The qPCR results showed trend of attenuated TNF-α mRNA expression in both SVF and ASCs treatment, and there was significantly reduced MCP-1 mRNA in SVF group. The mRNA expression of NF-κB p65, which is upstream of both TNF-α and MCP-1, was significantly suppressed in both groups. In addition, the application of ASC-derived exosomes also showed similar effects in increasing AVF lumen size and reducing α-SMA(+) cells as well as MCP-1 mRNA expression. In summary, both SVF and ASCs can effectively ameliorate AVF stenosis and might probably through the exosomes.

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