Background and Aims

The Extra-Uterine Environment for Neonatal Development (EXTEND) aims to avoid the complications of prematurity, such as NEC. Our goal was to determine if bowel development occurs normally in EXTEND-supported lambs, with specific emphasis on markers of immaturity associated with NEC.

Methods

We compared terminal ileum from 17 pre-term lambs supported on EXTEND for 2- 4 weeks to bowel from age-matched fetal lambs that developed in utero. We evaluated morphology, markers of epithelial integrity and maturation, enteric nervous system structure, and bowel motility.

Results

EXTEND-supported lamb ileum had normal villus height, crypt depth, density of mucin-containing goblet cells, and enteric neuron density. Expression patterns for I-FABP, activated caspase-3 and EGFR were normal in bowel epithelium. Transmural resistance assessed in Ussing chambers was normal. Bowel motility was also normal as assessed by ex vivo organ bath and video imaging. However, Peyer’s patch organization did not occur normally in EXTEND ileum, resulting in fewer circulating B cells in experimental animals.

Conclusion

EXTEND supports normal ileal epithelial and enteric nervous system maturation in pre-term lambs. The classic morphologic changes and cellular expression profiles associated with NEC are not seen. However, immune development within the EXTEND supported lamb bowel does not progress normally.

中文翻译：

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新生儿发育的宫外环境支持正常的肠道成熟和发育。

背景和目标

新生儿发育子宫外环境 (EXTEND) 旨在避免早产并发症，例如 NEC。我们的目标是确定 EXTEND 支持的羔羊肠道发育是否正常，特别强调与 NEC 相关的不成熟标志。

方法

我们将 EXTEND 支持 2-4 周的 17 只早产羔羊的末端回肠与子宫内发育的年龄匹配的胎儿羔羊的肠道进行了比较。我们评估了形态、上皮完整性和成熟的标志物、肠神经系统结构和肠蠕动。

结果

EXTEND支持的羔羊回肠具有正常的绒毛高度、隐窝深度、含粘蛋白杯状细胞的密度和肠神经元密度。肠上皮中 I-FABP、活化的 caspase-3 和 EGFR 的表达模式正常。在使用室中评估的透壁阻力是正常的。通过离体器官浴和视频成像评估，肠蠕动也正常。然而，派尔氏斑块组织在 EXTEND 回肠中并未正常发生，导致实验动物中循环 B 细胞减少。

结论

EXTEND 支持早产羔羊的正常回肠上皮和肠神经系统成熟。未观察到与 NEC 相关的经典形态变化和细胞表达谱。然而，EXTEND 支持的羊肠内的免疫发育不能正常进行。