284 - Human Wharton's jelly-derived mesenchymal stem cells improve sepsis-associated heart and lung injury

Cytotherapy(2017)

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摘要
Sepsis-related organ dysfunction is caused by a dysregulated host response to infection. Various preclinical studies have shown that Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have considerable therapeutic potential in inflammatory disorders. In comparison with stem cells from other sources, WJ-MSCs appear to have greater immunological and anti-apoptotic effects. We used a cecal ligation and puncture (CLP) model to analyze the role of WJ-MSCs in sepsis. We used flow cytometry to evaluate WJ-MSC phenotypes. We divided Wistar rats into groups: sham (sham-operated); CLP; and CLP+MSC (106 WJ-MSCs, i.p., 6 h after CLP). At 24 h post-surgery, we assessed haemodynamic and echocardiographic changes; evaluated lung injury; and performed immunoblotting for Toll-like receptor 4 (TLR4). For data comparison, we used one-way analysis of variance and the post hoc student–Newman–Keuls test, with a significance level of p < 0.05 in all tests. The WJ-MSCs were negative for CD3, CD34, CD45 and human leukocyte antigen-D region, whereas they were positive for CD73, CD90 and CD105. They also showed adipogenic, chondrogenic and osteogenic differentiation. The CLP rats developed diastolic heart failure with reduced cardiac output and pulmonary damage. Treatment with WJ-MSCs improved cardiovascular function and attenuated lung injury, as evidenced by decreased myeloperoxidase expression and apoptosis. In addition, the CLP+MSC rats showed TLR4 downregulation in the heart and spleen. It seems that WJ-MSCs protect against sepsis-related organ injury, reducing systemic inflammation and apoptosis.
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关键词
mesenchymal stem cells,stem cells,jelly-derived,sepsis-associated
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