Amniotic Epithelial Cells Accelerate Diabetic Wound Healing by Modulating Inflammation and Promoting Neovascularization.

Amniotic Epithelial Cells Accelerate Diabetic Wound Healing by Modulating Inflammation and Promoting Neovascularization.
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羊膜上皮细胞通过调节炎症和促进新血管形成来加速糖尿病伤口愈合。

DOI:
10.1155/2018/1082076
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发表时间:
2018
影响因子:
4.3
通讯作者:
Xia Z
Xia Z
中科院分区:
医学3区
文献类型:
--
作者:
Zheng Y;Zheng S;Fan X;Li L;Xiao Y;Luo P;Liu Y;Wang L;Cui Z;He F;Liu Y;Xiao S;Xia Z

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人羊膜上皮细胞(human amniotic epithelial cells,hAECs)具有非致瘤性、高丰度、低免疫原性和多向分化潜能,是再生医学理想的干细胞来源。先前的研究已经证明了hAEC在许多组织修复中的治疗潜力。然而,hAECs对糖尿病伤口愈合的治疗作用仍然未知。在这项研究中,我们在db/db小鼠的全层切除皮肤伤口周围皮内注射hAECs,发现hAECs显著加速糖尿病伤口愈合和肉芽组织形成。为了探索潜在的机制,我们测量了糖尿病伤口的炎症和新血管形成。hAECs可以调节巨噬细胞表型向M2巨噬细胞转化,促进伤口从促炎状态向促愈合状态的转变,并增加糖尿病伤口中的毛细血管密度。此外,我们发现hAEC条件培养基促进巨噬细胞向M2表型极化,并通过体外实验促进内皮细胞的迁移、增殖和管形成。综上所述,我们首次报道了hAEC可以促进糖尿病伤口愈合,至少部分是通过旁分泌作用来调节炎症和促进新血管形成。
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.
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