Cord Blood-Derived Endothelial Colony-Forming Cell Function is Disrupted in Congenital Diaphragmatic Hernia
Cord Blood-Derived Endothelial Colony-Forming Cell Function is Disrupted in Congenital Diaphragmatic Hernia
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先天性膈疝中脐带血来源的内皮集落形成细胞功能被破坏
DOI：
10.1152/ajplung.00357.2015
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发表时间：
2016
影响因子：
4.9
通讯作者：
Masahiko Kuroda
中科院分区：
文献类型：
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作者：
Hideshi Fujinaga;Hiroko Fujinaga;Nobuyuki Watanabe;Tomoko Kato;Moe Tamano;Miho Terao;Shuji Takada;Yushi Ito;Akihiro Umezawa;Masahiko Kuroda
血管生长对于肺的正常发育是必要的。虽然内皮祖细胞（EPCs）在血管形成中起着重要作用，但对先天性腹股沟疝（CDH）中的EPC功能知之甚少，CDH是一种与肺发育不良相关的严重新生儿疾病。我们假设，内皮细胞集落形成细胞（ECFC），一种类型的EPC，在CDH的功能受损。脐带血（CB）收集自足月CDH患者和健康对照。我们评估了CB祖细胞群以及血浆血管内皮生长因子（VEGF）和基质细胞衍生因子1α（SDF 1 α）水平。CB ECFC克隆形成;生长动力学;移民;还评估了VEGF、SDF 1 α和一氧化氮（NO）的产生;血管生成能力;以及VEGF-A、fms相关酪氨酸激酶1（FLT 1）、激酶插入结构域受体（KDR）、一氧化氮合酶（NOS）1-3、SDF 1和趋化因子（C-X-C基序）受体4（CXCR 4）的mRNA表达。与对照组相比，CDH组CBECFC减少。CDH ECFC具有降低的自我更新、克隆形成、增殖和迁移的潜力。CDH ECFC产生NO的能力增强，但对VEGF的反应减弱。CDH ECFC中新生血管发生的体内潜力降低。CDH和对照组之间CB血浆VEGF和SDF 1 α浓度、ECFC产生的VEGF和SDF 1 α以及ECFC VEGF-A、FLT 1、KDR、NOS 1 -3、SDF 1和CXCR 4的mRNA表达无差异。总之，CB ECFC功能在CDH中被破坏，但这些变化可能是由VEGF-NO和SDF 1-CXCR 4信号转导改变以外的机制引起的。
Vascular growth is necessary for normal lung development. Although endothelial progenitor cells (EPCs) play an important role in vascularization, little is known about EPC function in congenital diaphragmatic hernia (CDH), a severe neonatal condition that is associated with pulmonary hypoplasia. We hypothesized that the function of endothelial colony-forming cells (ECFCs), a type of EPC, is impaired in CDH. Cord blood (CB) was collected from full-term CDH patients and healthy controls. We assessed CB progenitor cell populations as well as plasma vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1α (SDF1α) levels. CB ECFC clonogenicity; growth kinetics; migration; production of VEGF, SDF1α, and nitric oxide (NO); vasculogenic capacity; and mRNA expression of VEGF-A, fms-related tyrosine kinase 1 (FLT1), kinase insert domain receptor (KDR), nitric oxide synthase (NOS) 1–3, SDF1, and chemokine (C-X-C motif) receptor 4 (CXCR4) were also assessed. Compared with controls, CB ECFCs were decreased in CDH. CDH ECFCs had reduced potential for self-renewal, clonogenicity, proliferation, and migration. Their capacity for NO production was enhanced but their response to VEGF was blunted in CDH ECFCs. In vivo potential for de novo vasculogenesis was reduced in CDH ECFCs. There was no difference in CB plasma VEGF and SDF1α concentrations, VEGF and SDF1α production by ECFCs, and ECFC mRNA expression of VEGF-A, FLT1, KDR, NOS1-3, SDF1, and CXCR4 between CDH and control subjects. In conclusion, CB ECFC function is disrupted in CDH, but these changes may be caused by mechanisms other than alteration of VEGF-NO and SDF1-CXCR4 signaling.