Novel bilayer cell patch combining epidermal stem cells and angiogenic adipose stem cells for diabetic wound healing.

Diabetic foot ulcer (DFU) is one of the most severe complications in patients with diabetes. However, the development of a promising therapeutic strategy for DFU is still challenging. In this article, we demonstrate a novel bilayer cell patch, and its therapeutic effects on diabetic wound healing have been systematically investigated. The experimental results revealed that diabetes mellitus exosomes (DM-Exos) could inhibit wound healing in normal C57/B6 mice. We identified three microRNAs (miRs) including miR-15a, miR-16, and miR-214 as anti-angiogenesis factors in DM-Exos. Furthermore, angiogenic-modified adipose stem cells (ADSCs, transfected with antagomiR-15a, antagomiR-16, and antagomiR-214) were found to enhance the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) by co-culture. In addition, our findings exhibited that the bilayer cell patch combining epidermal stem cells (EpSCs) and angiogenic-modified ADSCs transplantation could promote diabetic wound healing through enhancing angiogenesis and re-epithelization. These findings illustrate that the novel bilayer cell patch has great potential in diabetic wound healing.