■围产期炎症会增加早产儿支气管肺发育不良的风险,但是潜在的病理生理机制仍然未知。鉴于它们的抗炎和再生能力,多能成体祖细胞(MAPC)是一种有前景的基于细胞的疗法,可预防和/或治疗早产新生儿围产期炎症的肺部负面后果.因此,我们阐明了围产期炎症后不良早产肺部结局的病理生理学,以及在产前炎症和出生后通气暴露界面处MAPC治疗的肺部益处.
■在妊娠125天时,将仪器化的绵羊胎儿暴露于羊膜内脂多糖(LPS5mg),以诱发不良的全身和外周器官结局。在LPS暴露后两天静脉内施用MAPC(10×106个细胞)或盐水。在MAPC治疗后五天早产胎儿,并立即人道杀死或机械通气72小时。
■产前LPS暴露导致早产肺中的炎症和肺泡成熟减少。此外,暴露于LPS的通气羔羊表现出持续的肺部炎症和细胞连接丧失,并伴有肺水肿,最终导致更高的需氧量。MAPC治疗调节肺部炎症,防止上皮和内皮屏障的丧失,并改善子宫内的肺成熟。这些MAPC驱动的改进在出生后仍然很明显,并预防伴随的肺水肿和功能丧失。
■总而言之,产前炎症使不发达的早产肺对随后的产后炎症敏感,造成伤害,发育障碍和功能障碍。MAPC治疗可部分预防这些变化,因此是早产儿预防不良肺部结局的有希望的方法。
UNASSIGNED: Perinatal inflammation increases the risk for bronchopulmonary dysplasia in preterm neonates, but the underlying pathophysiological mechanisms remain largely unknown. Given their anti-inflammatory and regenerative capacity, multipotent adult progenitor cells (MAPC) are a promising cell-based therapy to prevent and/or treat the negative pulmonary consequences of perinatal inflammation in the preterm neonate. Therefore, the pathophysiology underlying adverse preterm lung outcomes following perinatal inflammation and pulmonary benefits of MAPC treatment at the interface of prenatal inflammatory and postnatal ventilation exposures were elucidated.
UNASSIGNED: Instrumented ovine fetuses were exposed to intra-amniotic lipopolysaccharide (LPS 5 mg) at 125 days gestation to induce adverse systemic and peripheral organ outcomes. MAPC (10 × 106 cells) or saline were administered intravenously two days post LPS exposure. Fetuses were delivered preterm five days post MAPC treatment and either killed humanely immediately or mechanically ventilated for 72 h.
UNASSIGNED: Antenatal LPS exposure resulted in inflammation and decreased alveolar maturation in the preterm lung. Additionally, LPS-exposed ventilated lambs showed continued pulmonary inflammation and cell junction loss accompanied by pulmonary edema, ultimately resulting in higher oxygen demand. MAPC therapy modulated lung inflammation, prevented loss of epithelial and endothelial barriers and improved lung maturation in utero. These MAPC-driven improvements remained evident postnatally, and prevented concomitant pulmonary edema and functional loss.
UNASSIGNED: In conclusion, prenatal inflammation sensitizes the underdeveloped preterm lung to subsequent postnatal inflammation, resulting in injury, disturbed development and functional impairment. MAPC therapy partially prevents these changes and is therefore a promising approach for preterm infants to prevent adverse pulmonary outcomes.