305-OR: Quiescence Abrogates Stress-Induced Senescence-Associated Secretion Phenotype in Adipose-Derived Stem Cells and May Enhance Their Therapeutic Effects on Diabetic Complications Free

The anti-inflammatory functions of adipose-derived stem cells (ADSC) are receiving much attention as potential treatment for diabetic complications, although it is not yet established. Cellular stresses render ADSC prematurely senescent, in which senescent ADSC propagate instead of suppressing inflammation in neighboring cells and tissues through their secretory profile, which is called senescence-associated secretion phenotype (SASP) . In diabetes, ADSC exhibit SASP, which decreases the feasibility of ADSC-based therapies. We previously reported that ADSC become quiescent when cultured on a substrate whose stiffness mimics that of adipose tissue. Here, we investigated the effect of quiescence on high glucose-induced SASP in ADSC. When cultured in three-dimensional (3D) gels, ADSC became quiescent and showed upregulated indolemine 2,3-dioxygene in response to tumor necrosis factor α and interferon γ stimulation to mimic inflammation ex vivo. High glucose treatment upregulated MCP-1 in ADSC cultured on plastic tissue culture plates, and their conditioned medium decreased the viability of HUVEC, an endothelial cell line. However, even under high glucose conditions, transferring ADSC from plastic to 3D gels attenuated MCP-1 expression, and their conditioned medium restored the viability of HUVEC. Transplantation of gels containing ADSC into mice resulted in vascular formation in those gels, and enhanced wound healing was suggested. These results open up the possibility that quiescence will eliminate SASP in ADSC even under hyperglycemia and promote the ability of ADSC to have therapeutic effects on diabetic complications.