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人间充质干细胞通过抗氧化过程、血管保护、肝细胞分化和营养作用来保护肝脏免受辐射损伤。

Human mesenchymal stem cells provide protection against radiation-induced liver injury by antioxidative process, vasculature protection, hepatocyte differentiation, and trophic effects.

作者信息

Francois Sabine, Mouiseddine Moubarak, Allenet-Lepage Bénédicte, Voswinkel Jan, Douay Luc, Benderitter Marc, Chapel Alain

机构信息

Laboratoire de Radiopathologie et de Thérapies Expérimentales (LRTE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM/SRBE/LRTE, BP 17, F-92262 Fontenay-aux-Roses Cedex, France ; UMRS-938, Equipe Prolifération et Différenciation des Cellules Souches du Pr Luc Douay: Application à la Thérapie Cellulaire, Faculté de Médecine Saint-Antoine, Université Paris VI Pierre et Marie Curie, 27 rue de Chaligny, 75012 Paris, France.

Laboratoire de Radiopathologie et de Thérapies Expérimentales (LRTE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM/SRBE/LRTE, BP 17, F-92262 Fontenay-aux-Roses Cedex, France.

出版信息

Biomed Res Int. 2013;2013:151679. doi: 10.1155/2013/151679. Epub 2013 Nov 28.

Abstract

To evaluate the potential therapeutic effect of the infusion of hMSCs for the correction of liver injuries, we performed total body radiation exposure of NOD/SCID mice. After irradiation, mir-27b level decreases in liver, increasing the directional migration of hMSCs by upregulating SDF1 α . A significant increase in plasmatic transaminases levels, apoptosis process in the liver vascular system, and in oxidative stress were observed. hMSC injection induced a decrease in transaminases levels and oxidative stress, a disappearance of apoptotic cells, and an increase in Nrf2, SOD gene expression, which might reduce ROS production in the injured liver. Engrafted hMSCs expressed cytokeratin CK18 and CK19 and AFP genes indicating possible hepatocyte differentiation. The presence of hMSCs expressing VEGF and Ang-1 in the perivascular region, associated with an increased expression of VEGFr1, r2 in the liver, can confer a role of secreting cells to hMSCs in order to maintain the endothelial function. To explain the benefits to the liver of hMSC engraftment, we find that hMSCs secreted NGF, HGF, and anti-inflammatory molecules IL-10, IL1-RA contributing to prevention of apoptosis, increasing cell proliferation in the liver which might correct liver dysfunction. MSCs are potent candidates to repair and protect healthy tissues against radiation damages.

摘要

为了评估输注人骨髓间充质干细胞(hMSCs)对纠正肝损伤的潜在治疗效果,我们对NOD/SCID小鼠进行了全身辐射暴露。辐射后,肝脏中mir-27b水平降低,通过上调SDF1α增加了hMSCs的定向迁移。观察到血浆转氨酶水平显著升高、肝血管系统中的凋亡过程以及氧化应激增加。注射hMSCs导致转氨酶水平和氧化应激降低、凋亡细胞消失以及Nrf2、SOD基因表达增加,这可能减少受损肝脏中的活性氧生成。植入的hMSCs表达细胞角蛋白CK18和CK19以及AFP基因,表明可能发生肝细胞分化。在血管周围区域存在表达VEGF和Ang-1的hMSCs,与肝脏中VEGFr1、r2表达增加相关,这可以赋予hMSCs分泌细胞的作用以维持内皮功能。为了解释hMSC植入对肝脏的益处,我们发现hMSCs分泌NGF、HGF和抗炎分子IL-10、IL1-RA,有助于预防凋亡,增加肝脏中的细胞增殖,这可能纠正肝功能障碍。间充质干细胞是修复和保护健康组织免受辐射损伤的有力候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df03/3863471/bd426e991733/BMRI2013-151679.001.jpg

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