Histological and Physiological Studies of the Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Bleomycin Induced Lung Fibrosis in Adult Albino Rats.

IF 5.5 3区 材料科学 Q2 CHEMISTRY, PHYSICAL ACS Applied Energy Materials Pub Date : 2021-02-01 Epub Date: 2020-10-22 DOI:10.1007/s13770-020-00294-0
Dina Mohamed Zakaria, Noha Mahmoud Zahran, Samia Abdel Aziz Arafa, Radwa Ali Mehanna, Rehab Ahmed Abdel-Moneim
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Abstract

Background: Lung fibrosis is considered as an end stage for many lung diseases including lung inflammatory disease, autoimmune diseases and malignancy. There are limited therapeutic options with bad prognostic outcome. The aim of this study was to explore the effect of mesenchymal stem cells (MSCs) derived from bone marrow on Bleomycin (BLM) induced lung fibrosis in albino rats.

Methods: 30 adult female albino rats were distributed randomly into 4 groups; negative control group, Bleomycin induced lung fibrosis group, lung fibrosis treated with bone marrow-MSCs (BM-MSCs) and lung fibrosis treated with cell free media. Lung fibrosis was induced with a single dose of intratracheal instillation of BLM. BM-MSCs or cell free media were injected intravenously 28 days after induction and rats were sacrificed after another 28 days for assessment. Minute respiratory volume (MRV), forced vital capacity (FVC) and forced expiratory volume 1 (FEV1) were recorded using spirometer (Power lab data acquisition system). Histological assessment was performed by light microscopic examination of H&E, and Masson's trichrome stained sections and was further supported by morphometric studies. In addition, electron microscopic examination to assess ultra-structural changes was done. Confocal Laser microscopy and PCR were used as tools to ensure MSCs homing in the lung.

Results: Induction of lung fibrosis was confirmed by histological examination, which revealed disorganized lung architecture, thickened inter-alveolar septa due excessive collagen deposition together with inflammatory cellular infiltration. Moreover, pneumocytes depicted variable degenerative changes. Reduction in MRV, FVC and FEV1 were recorded. BM-MSCs treatment showed marked structural improvement with minimal cellular infiltration and collagen deposition and hence restored lung architecture, together with lung functions.

Conclusion: MSCs are promising potential therapy for lung fibrosis that could restore the normal structure and function of BLM induced lung fibrosis.

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骨髓间充质干细胞对博莱霉素诱导的成年白化大鼠肺纤维化影响的组织学和生理学研究
背景:肺纤维化被认为是许多肺部疾病(包括肺部炎症性疾病、自身免疫性疾病和恶性肿瘤)的终末阶段。目前的治疗方案有限,且预后不良。方法:将30只成年雌性白化大鼠随机分为4组:阴性对照组、博莱霉素诱导肺纤维化组、骨髓间充质干细胞(BM-MSCs)治疗肺纤维化组和无细胞培养基治疗肺纤维化组。单剂量气管内灌注博莱霉素诱导肺纤维化。诱导28天后静脉注射BM-间充质干细胞或无细胞培养基,28天后将大鼠处死以进行评估。使用肺活量计(Power lab 数据采集系统)记录分钟呼吸量(MRV)、用力呼吸量(FVC)和用力呼气量 1(FEV1)。组织学评估通过 H&E 和 Masson 三色染色切片的光镜检查进行,并进一步辅以形态计量学研究。此外,还进行了电子显微镜检查,以评估超结构变化。激光共聚焦显微镜和 PCR 被用作确保间充质干细胞在肺部归巢的工具:组织学检查证实,间充质干细胞诱导了肺纤维化,显示出肺部结构紊乱,肺泡间隙因胶原过度沉积而增厚,并伴有炎性细胞浸润。此外,肺细胞也出现了不同程度的退行性变化。MRV、FVC和FEV1均有所下降。BM 间充质干细胞治疗可明显改善肺部结构,减少细胞浸润和胶原沉积,从而恢复肺部结构和肺功能:结论:间充质干细胞是治疗肺纤维化的一种很有前景的潜在疗法,它能恢复 BLM 诱导的肺纤维化的正常结构和功能。
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来源期刊
ACS Applied Energy Materials
ACS Applied Energy Materials Materials Science-Materials Chemistry
CiteScore
10.30
自引率
6.20%
发文量
1368
期刊介绍: ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.
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