Abstract
Human amniotic epithelial cells (hAECs) are nontumorigenic, highly abundant, and low immunogenic and possess multipotent differentiation ability, which make them become ideal alternative stem cell source for regenerative medicine. Previous studies have demonstrated the therapeutic potential of hAECs in many tissue repairs. However, the therapeutic effect of hAECs on diabetic wound healing is still unknown. In this study, we injected hAECs intradermally around the full-thickness excisional skin wounds of db/db mice and found that hAECs significantly accelerated diabetic wound healing and granulation tissue formation. To explore the underlying mechanisms, we measured inflammation and neovascularization in diabetic wounds. hAECs could modulate macrophage phenotype toward M2 macrophage, promote switch from proinflammatory status to prohealing status of wounds, and increase capillary density in diabetic wounds. Furthermore, we found that the hAEC-conditioned medium promoted macrophage polarization toward M2 phenotype and facilitated migration, proliferation, and tube formation of endothelial cells through in vitro experiments. Taken together, we first reported that hAECs could promote diabetic wound healing, at least partially, through paracrine effects to regulate inflammation and promote neovascularization.
Highlights
Diabetic ulcers are a severe, resistant complication of diabetes mellitus (DM), and about one fourth of DM patients endure diabetic lower extremity ulcers during their whole lives [1]
At day 10, the wound healing rate was significantly higher in the Human amniotic epithelial cells (hAECs)-treated group (52.16 ± 6.80%) than that in the PBS-treated group (35.76 ± 6.19%, P < 0 001, Figure 1(b))
Using iNOS as a marker of M1 macrophage and CD206 as a marker of M2 macrophage, we found that hAEC-treated wounds had fewer M1 macrophages (Figure 3(b)), more M2 macrophages (Figure 3(c)), and a significantly lower M1/M2 ratio (Figure 3(d))
Summary
Diabetic ulcers are a severe, resistant complication of diabetes mellitus (DM), and about one fourth of DM patients endure diabetic lower extremity ulcers during their whole lives [1]. Diabetic wounds tend to heal slowly and be frequently recurrent, leading to increasing cost of medical care and seriously impairing the quality of life in diabetic patients. Mesenchymal stem cell (MSC) is one of the most widely studied stem cells for wound healing, and several studies have demonstrated inspiring preclinical results through animal models [2,3,4,5]. Human amniotic epithelial cells (hAECs) are derived from the amniotic membrane and demonstrate a potential source of stem cells. These cells are nontumorigenic and low immunogenic and possess multipotent differentiation ability [6,7,8]. HAECs are highly plentiful, and about 1.5 × 108 cells could be separated
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