Lee Jasmine, Joseph Sharon, Manohar Krishna, Mesfin Fikir, Hunter Chelsea, Brokaw John, Shelley W Chris, Liu Jianyun, McCain Robyn, Crain Christa J, Lescun Timothy, Markel Troy A
Indiana University School of Medicine.
Purdue University.
Res Sq. 2025 Aug 18:rs.3.rs-7285196. doi: 10.21203/rs.3.rs-7285196/v1.
Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disease of prematurity characterized by inflammation, necrosis, and high morbidity. Current therapies are limited, necessitating the development of novel treatments. Mesenchymal stromal cells (MSCs) have shown promise in murine NEC models. Given the anatomical and physiological similarities between premature piglets and human infants, we employed a preterm piglet model to evaluate MSC efficacy. We hypothesized that intraperitoneal MSC administration would reduce intestinal injury in NEC.
Preterm piglets were delivered via cesarean section. NEC was induced on day 3 through hypertonic enteral feeding. MSCs were administered intraperitoneally at low, medium, or high doses. Piglets were monitored and euthanized based on clinical criteria. Clinical scores, weight change, gross and histologic intestinal injuries were assessed. Cytokine levels in serum and ileum were quantified via ELISA, and intestinal tissue was analyzed by RNA sequencing. Statistical significance was set at p < 0.05.
Medium-dose MSCs significantly improved clinical scores and reduced both gross and histologic intestinal injury (p < 0.05). A corresponding decrease in pro-inflammatory cytokines was observed.
This is the first study to demonstrate therapeutic benefit of MSCs in a preterm piglet NEC model, supporting their potential use in translational NEC therapies.
坏死性小肠结肠炎（NEC）是一种危及生命的早产儿胃肠道疾病，其特征为炎症、坏死和高发病率。目前的治疗方法有限，因此需要开发新的治疗方法。间充质基质细胞（MSC）在小鼠NEC模型中已显示出前景。鉴于早产仔猪与人类婴儿在解剖学和生理学上的相似性，我们采用早产仔猪模型来评估MSC的疗效。我们假设腹腔内给予MSC可减轻NEC中的肠道损伤。
通过剖宫产分娩早产仔猪。在第3天通过高渗肠内喂养诱导NEC。以低、中、高剂量腹腔内给予MSC。根据临床标准对仔猪进行监测并实施安乐死。评估临床评分、体重变化、大体和组织学肠道损伤。通过ELISA定量血清和回肠中的细胞因子水平，并通过RNA测序分析肠道组织。统计学显著性设定为p < 0.05。
中等剂量的MSC显著改善了临床评分，并减轻了大体和组织学肠道损伤（p < 0.05）。观察到促炎细胞因子相应减少。
这是第一项证明MSC在早产仔猪NEC模型中具有治疗益处的研究，支持了其在NEC转化治疗中的潜在应用。
