Oral administration of bone marrow-derived mesenchymal stem cells attenuates intestinal injury in necrotizing enterocolitis.

IF 3.2 Q1 PEDIATRICS
Clinical and Experimental Pediatrics Pub Date : 2024-03-01 Epub Date: 2024-02-19 DOI:10.3345/cep.2023.01151
Yeong Seok Lee, Yong Hoon Jun, Juyoung Lee
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Abstract

Background: Necrotizing enterocolitis (NEC) is a major cause of morbidity in premature infants. However, effective treatment options for NEC are currently lacking.

Purpose: This study aimed to determine the optimal dose of intraperitoneally administered bone marrow-derived mesenchymal stem cells (BM-MSCs) and investigate the therapeutic potential of orally administered BM-MSCs in NEC.

Methods: Neonatal mice were fed maternal breast milk for the first 2 days of life. On day 3, the neonatal mice were randomly divided into control, negative control, and BM-MSC-treated groups. Lipopolysaccharide (LPS) was administered for 3 days, and cold stress (4°C, 10 minutes) was applied 3 times a day to induce NEC. High-dose (1×106 cells) or low-dose (1×105 cells) BM-MSCs were administered intraperitoneally 1 or 3 times between days 6 and 8 to treat the NEC. The orally administered group received a low dose of BM-MSCs on day 6. Furthermore, except for the control group, intraepithelial cells (IECs) of the small intestine of neonatal mice were treated with LPS and exposed to 5% O2/95% N2 hypoxic stress for 2 hours. Thereafter, each was treated with BM-MSCs.

Results: Tissue injury, apoptosis, and inflammatory marker levels were significantly reduced after BM-MSC administration. Oral administration was as effective as intraperitoneal administration, even at a low dose (1×105 cells) of BM-MSCs. The efficacy of high (1×106 cells) or multiple divided doses of BM-MSCs did not differ from that of low-dose treatment. Significantly improved wound healing was observed after BM-MSC administration to injured IECs.

Conclusion: The oral administration of BM-MSCs is a promising treatment option for NEC in infants. Further human studies of BM-MSCs are necessary to determine the optimal dose required to achieve safe and effective outcomes.

口服骨髓间充质干细胞可减轻坏死性小肠结肠炎的肠道损伤。
背景: :坏死性小肠结肠炎(NEC)是早产儿发病的主要原因。目的:本研究旨在确定腹腔注射骨髓间充质干细胞的最佳剂量:本研究旨在确定腹腔注射骨髓间充质干细胞(BM-MSCs)的最佳剂量,并探讨口服骨髓间充质干细胞治疗坏死性小肠结肠炎的潜力:方法:新生小鼠出生后头两天喂母乳。第3天,新生小鼠被随机分为对照组、阴性对照组和BM-间充质干细胞治疗组。给新生小鼠注射脂多糖(LPS)3 天,每天施加 3 次冷应激(4°C,10 分钟)以诱发 NEC。在第6天和第8天之间,腹腔注射高剂量(1×106个细胞)或低剂量(1×105个细胞)BM-间充质干细胞1次或3次,以治疗NEC。口服组在第6天接受低剂量的BM-间充质干细胞。此外,除对照组外,新生小鼠的小肠上皮内细胞(IECs)均经 LPS 处理,并暴露于 5% O2/95% N2 的缺氧压力下 2 小时。之后,分别用骨髓间充质干细胞进行处理:给小鼠注射骨髓间充质干细胞后,组织损伤、细胞凋亡和炎症标志物水平明显降低。即使是低剂量(1×105 个细胞)的 BM-间充质干细胞,口服给药与腹腔给药同样有效。高剂量(1×106 个细胞)或多次分次给药 BM-MSCs 的疗效与低剂量治疗没有差异。结论:口服 BM-MSCs 对损伤的 IECs 有显著的伤口愈合效果:结论:口服 BM-MSCs 是一种治疗婴儿 NEC 的有效方法。有必要对 BM-MSCs 进行进一步的人体研究,以确定达到安全有效治疗效果所需的最佳剂量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.00
自引率
2.40%
发文量
88
审稿时长
60 weeks
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