Overexpressing HPGDS in adipose-derived mesenchymal stem cells reduces inflammatory state and improves wound healing in type 2 diabetic mice

Background In diabetes, delayed wound healing was considered as the result of excessive recruitment and retention of pro-inflammatory cells and factors. Hematopoietic prostaglandin D synthase (HPGDS) was identified from differently expressed genes of diabetic human foot skin. HPGDS is responsible for the production of prostaglandin D2 (PGD2), an inflammatory mediator. Therefore, we aim to explore whether HPGDS could be a therapeutic target in the diabetic wound (DW). Method In this study, we compared gene expression profilings of diabetic human foot skin and non-diabetic human foot skin from the Gene Expression Omnibus database. We detected the characteristics of immune components in diabetic mice wound and investigated the role and underlying mechanism of the differently expressed Hpgds for the diabetic wound healing. For in vivo studies, we engineered ADSC to overexpress Hpgds (ADSC.sup.Hpgds) and evaluated its effects on diabetic wound healing using a full-thickness skin wound model. For in vitro studies, we evaluated the role of ADSC.sup.Hpgds conditioned medium and PGD2 on Lipopolysaccharide (LPS) induced macrophage. Results Hpgds was significantly down-regulated in type 2 diabetic mice wound and its deficiency delayed normal wound healing. ADSC.sup.Hpgds accelerated DW healing by reducing neutrophil and CD8T cell recruitment, promoting M2 macrophage polarization and increasing the production of growth factors. ADSC.sup.Hpgds conditioned medium showed superior capability in promoting M2 macrophage transition than conditioned medium derived from ADSC alone. Conclusion Our results demonstrated that Hpgds is required for wound healing, and ADSC.sup.Hpgds could accelerate DW healing by improving anti-inflammatory state and normalizing the proliferation phase of wound healing in mice. These findings provide a new insight in the therapeutic strategy of diabetic wound. Keywords: Hpgds, Diabetic wound, ADSC, Inflammation regulator, Healing