Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
J Pediatr Surg. 2020 Feb;55(2):249-252. doi: 10.1016/j.jpedsurg.2019.10.033. Epub 2019 Nov 9.
We sought to determine whether TRASCET could impact congenital diaphragmatic hernia (CDH).
Twelve pregnant dams received Nitrofen on gestational day 9.5 (E9; term = 22 days) to induce fetal CDH. Fetuses were divided into three groups: untreated (n = 31) and two groups receiving volume-matched intraamniotic injections of either saline (n = 37) or a suspension of 2 × 10 cells/mL of amniotic fluid-derived mesenchymal stem cells (afMSCs; n = 65) on E17. Animals were euthanized at term. Expression of fibroblast growth factor-10 (FGF-10), vascular endothelial growth factor-A (VEGF-A), and surfactant protein-C (SPC) was quantified by qRT-PCR. Statistical analysis was by the Mann-Whitney U test with Bonferroni adjusted criterion (p ≤ 0.01).
Among survivors with CDH (n = 27/133), the TRASCET group showed significant downregulation of FGF-10 and VEGF-A gene expressions compared to the untreated (p < 0.001 for both) and saline groups (p = 0.005 and p = 0.004, respectively). SPC expression was higher in the TRASCET group compared to the untreated group (p = 0.01), but not the saline group (p = 0.043). Lung laterality had minimal impact on these comparisons.
Transamniotic stem cell therapy affects select processes of lung development in experimental congenital diaphragmatic hernia. Further scrutiny into this novel therapy as a potential component of the prenatal management of this disease is warranted.
N/A (animal and laboratory study).
我们旨在确定 TRASCET 是否能影响先天性膈疝（CDH）。
12 只怀孕的母鼠在妊娠第 9.5 天（E9；足月=22 天）接受 Nitrofen，以诱导胎儿 CDH。胎儿分为三组：未治疗组（n=31）和两组接受体积匹配的羊水来源间充质干细胞（afMSCs）悬液的宫内注射，分别为生理盐水组（n=37）和 2×10 细胞/ml afMSCs 组（n=65），注射时间为 E17。动物在足月时安乐死。通过 qRT-PCR 定量检测成纤维细胞生长因子 10（FGF-10）、血管内皮生长因子-A（VEGF-A）和表面活性蛋白-C（SPC）的表达。统计分析采用 Mann-Whitney U 检验，并用 Bonferroni 调整标准（p≤0.01）。
在幸存者中 CDH（n=133 例中的 27 例），TRASCET 组与未治疗组（均为 p<0.001）和生理盐水组（分别为 p=0.005 和 p=0.004）相比，FGF-10 和 VEGF-A 基因表达显著下调。与未治疗组相比，TRASCET 组 SPC 表达更高（p=0.01），但与生理盐水组无差异（p=0.043）。肺的侧别对这些比较的影响最小。
经羊膜腔内干细胞治疗可影响实验性先天性膈疝中肺发育的某些过程。进一步研究这种新型治疗方法作为该疾病产前管理的潜在组成部分是有必要的。
无（动物和实验室研究）。
