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间质干细胞:在急性呼吸窘迫综合征的实验模型中是否有效?

Mesenchymal stem cell: does it work in an experimental model with acute respiratory distress syndrome?

机构信息

Department of Pediatric Hematology/Oncology, Ondokuz Mayıs University Faculty of Medicine, 55220, Atakum, Samsun, Turkey.

出版信息

Stem Cell Rev Rep. 2013 Feb;9(1):80-92. doi: 10.1007/s12015-012-9395-2.

Abstract

We hypothesized that bone marrow-derived mesenchymal stem cells (BM-MSCs) would have a possible role in the treatment of acute respiratory distress syndrome (ARDS). ARDS disease model was developed in Wistar albino male rats by intratracheal instillation of physiological saline solution. Anesthezied and tracheotomized rats (n = 8) with ARDS were pressure-controlled ventilated. Isolated and characterized rat (r-) BM-MSCs were labeled with GFP gene, and introduced in the lungs of the ARDS rat-model. After applying of MSCs, the life span of each rat was recorded. When rats died, their lung tissues were removed for histopathological examination. Also the tissue sections were analyzed for GFP labeled rBM-MSCs and stained for vimentin, CK19, proinflammatory (MPO, IL-1β, IL-6 and MIP-2) and anti-inflammatory [IL-1ra and prostaglandin E2 receptor (EP3)] cytokines. The histopathological signs of rat-model ARDS were similar to the acute phase of ARDS in humans. rBM-MSCs were observed to home in lung paranchyma. Although the infiltration of neutrophils slightly decreased in the interalveolar, peribronchial and perivascular area, a notable improvement was determined in the degree of hemorrhage, edema and hyaline membrane formation in rats treated with rBM-MSCs. Also decreased proinflammatory cytokines levels and increased the intensity of anti-inflammatory cytokines were established. Therefore MSCs could promote alveolar epithelial repair by mediating of cytokines from a proinflammatory to an anti-inflammatory response. As a novel therapeutic approach, mesenchymal stem cell treatment with intratracheal injection could be helpful in the management of critically ill patients with ARDS.

摘要

我们假设骨髓间充质干细胞(BM-MSCs)可能在急性呼吸窘迫综合征(ARDS)的治疗中发挥作用。通过气管内滴注生理盐水建立 Wistar 白化雄性大鼠 ARDS 疾病模型。麻醉并气管切开 ARDS 大鼠(n = 8),进行压力控制通气。分离和鉴定大鼠(r-)BM-MSCs 并标记 GFP 基因,然后将其引入 ARDS 大鼠模型的肺部。应用 MSC 后,记录每只大鼠的存活时间。当大鼠死亡时,取出其肺组织进行组织病理学检查。还分析了组织切片中的 GFP 标记 rBM-MSCs 以及用于波形蛋白、CK19、促炎(MPO、IL-1β、IL-6 和 MIP-2)和抗炎[IL-1ra 和前列腺素 E2 受体(EP3)]细胞因子的染色。大鼠模型 ARDS 的组织病理学特征与人类 ARDS 的急性期相似。rBM-MSCs 被观察到归巢到肺实质中。尽管在肺泡间、支气管周围和血管周围区域中性粒细胞浸润略有减少,但在接受 rBM-MSCs 治疗的大鼠中,出血、水肿和透明膜形成的程度有明显改善。还确定了促炎细胞因子水平降低和抗炎细胞因子强度增加。因此,MSC 可以通过介导从促炎到抗炎的细胞因子反应来促进肺泡上皮修复。作为一种新的治疗方法,气管内注射间充质干细胞治疗可能有助于 ARDS 危重症患者的管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7764/9516527/39a170d1171a/12015_2012_9395_Fig1_HTML.jpg

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