Mesenchymal stem cells against intestinal ischemia-reperfusion injury: a systematic review and meta-analysis of preclinical studies

间充质干细胞对抗肠缺血再灌注损伤:临床前研究的系统评价和荟萃分析

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Abstract

BACKGROUND: Intestinal ischemia-reperfusion injury (IRI) causes localized and distant tissue lesions. Multiple organ failure is a common complication of severe intestinal IRI, leading to its high rates of morbidity and mortality. Thus far, this is poorly treated, and there is an urgent need for new more efficacious treatments. This study evaluated the beneficial effects of mesenchymal stem cells (MSCs) therapy on intestinal IRI using many animal experiments. METHODS: We conducted a comprehensive literature search from 4 databases: Pubmed, Embase, Cochrane library, and Web of science. Primary outcomes included the survival rate, Chiu's score, intestinal levels of IL-6, TNF-α and MDA, as well as serum levels of DAO, D-Lactate, and TNF-α. Statistical analysis was carried out using Review Manager 5.3. RESULTS: It included Eighteen eligible researches in the final analysis. We demonstrated that survival rates in animals following intestinal IRI were higher with MSCs treatment compared to vehicle treatment. Besides, MSCs treatment attenuated intestinal injury caused by IRI, characterized by lower Chiu's score (- 1.96, 95% CI - 2.72 to - 1.19, P < 0.00001), less intestinal inflammation (IL-6 (- 2.73, 95% CI - 4.19 to - 1.27, P = 0.0002), TNF-α (- 3.00, 95% CI - 4.74 to - 1.26, P = 0.0007)) and oxidative stress (MDA (- 2.18, 95% CI - 3.17 to - 1.19, P < 0.0001)), and decreased serum levels of DAO (- 1.39, 95% CI - 2.07 to - 0.72, P < 0.0001), D-Lactate (- 1.54, 95% CI - 2.18 to - 0.90, P < 0.00001) and TNF-α (- 2.42, 95% CI - 3.45 to - 1.40, P < 0.00001). The possible mechanism for MSCs to treat intestinal IRI might be through reducing inflammation, alleviating oxidative stress, as well as inhibiting the apoptosis and pyroptosis of the intestinal epithelial cells. CONCLUSIONS: Taken together, these studies revealed that MSCs as a promising new treatment for intestinal IRI, and the mechanism of which may be associated with inflammation, oxidative stress, apoptosis, and pyroptosis. However, further studies will be required to confirm these findings.

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