Zhu Dandan, Muljadi Ruth, Chan Siow Teng, Vosdoganes Patricia, Lo Camden, Mockler Joanne C, Wallace Euan M, Lim Rebecca
The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Clayton, VIC, Australia; Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia.
Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia.
Stem Cells Int. 2016;2016:4565612. doi: 10.1155/2016/4565612. Epub 2015 Dec 29.
The effects of human amnion epithelial cells (hAECs) on angiogenesis remain controversial. It is yet unknown if the presence of inflammation and/or gestational age of hAEC donors have an impact on angiogenesis. In this study, we examined the differences between term and preterm hAECs on angiogenesis in vitro and in vivo. Conditioned media from term hAECs induced the formation of longer huVEC tubules on Matrigel. Both term and preterm hAECs expressed VEGFA, PDGFB, ANGPT1, and FOXC1, which significantly increased after TNFα and IFNγ stimulation. In the presence of TNFα and IFNγ, coculture with term hAECs reduced gene transcription of Tie-2 and Foxc1 in huVECs, while coculture with preterm hAECs increased gene transcription of PDGFRα and PDGFRβ and reduced gene transcription of FOXC1 in huVECs. In vivo assessment of angiogenesis using vWF immunostaining revealed that hAEC treatment decreased angiogenesis in a bleomycin model of lung fibrosis but increased angiogenesis in a neonatal model of hyperoxia-induced lung injury. In summary, our findings suggested that the impact of hAECs on angiogenesis may be influenced by the presence of inflammation and underlying pathology.
人羊膜上皮细胞（hAECs）对血管生成的影响仍存在争议。hAEC供体的炎症状态和/或胎龄是否会对血管生成产生影响尚不清楚。在本研究中，我们检测了足月和早产hAECs在体外和体内血管生成方面的差异。足月hAECs的条件培养基可诱导Matrigel上形成更长的人脐静脉内皮细胞（huVEC）微管。足月和早产hAECs均表达血管内皮生长因子A（VEGFA）、血小板衍生生长因子B（PDGFB）、血管生成素1（ANGPT1）和叉头框蛋白C1（FOXC1），在肿瘤坏死因子α（TNFα）和干扰素γ（IFNγ）刺激后显著增加。在TNFα和IFNγ存在的情况下，与足月hAECs共培养可降低huVECs中Tie-2和Foxc1的基因转录，而与早产hAECs共培养则增加huVECs中血小板衍生生长因子受体α（PDGFRα）和血小板衍生生长因子受体β（PDGFRβ）的基因转录，并降低FOXC1的基因转录。使用血管性血友病因子（vWF）免疫染色对血管生成进行体内评估显示，hAEC治疗在博来霉素诱导的肺纤维化模型中减少了血管生成，但在高氧诱导的新生儿肺损伤模型中增加了血管生成。总之，我们的研究结果表明，hAECs对血管生成的影响可能受炎症状态和潜在病理状况的影响。
