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骨髓间充质干细胞单次注射可控制 BALB/c 小鼠过敏性哮喘肺组织损伤,注射时间可延迟至移植后 14 天。

Lung Tissue Damage Associated with Allergic Asthma in BALB/c Mice Could Be Controlled with a Single Injection of Mesenchymal Stem Cells from Human Bone Marrow up to 14 d After Transplantation.

机构信息

Core for Cell Technology, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná, Brazil.

Department of Animal Science, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná, Brazil.

出版信息

Cell Transplant. 2020 Jan-Dec;29:963689720913254. doi: 10.1177/0963689720913254.

Abstract

Mesenchymal stem cell (MSC) research has demonstrated the potential of these cells to modulate lung inflammatory processes and tissue repair; however, the underlying mechanisms and treatment durability remain unknown. Here, we investigated the therapeutic potential of human bone marrow-derived MSCs in the inflammatory process and pulmonary remodeling of asthmatic BALB/c mice up to 14 d after transplantation. Our study used ovalbumin to induce allergic asthma in male BALB/c mice. MSCs were injected intratracheally in the asthma groups. Bronchoalveolar lavage fluid (BALF) was collected, and cytology was performed to measure the total protein, hydrogen peroxide (HO), and proinflammatory (IL-5, IL-13, and IL-17A) and anti-inflammatory (IL-10) interleukin (IL) levels. The lungs were removed for the histopathological evaluation. On day zero, the eosinophil and lymphochte percentages, total protein concentrations, and IL-13 and IL-17A levels in the BALF were significantly increased in the asthma group, proving the efficacy of the experimental model of allergic asthma. On day 7, the MSC-treated group exhibited significant reductions in the eosinophil, lymphocyte, total protein, HO, IL-5, IL-13, and IL-17A levels in the BALF, while the IL-10 levels were significantly increased. On day 14, the total cell numbers and lymphocyte, total protein, IL-13, and IL-17A levels in the BALF in the MSC-treated group were significantly decreased. A significant decrease in airway remodeling was observed on days 7 and 14 in almost all bronchioles, which showed reduced inflammatory infiltration, collagen deposition, muscle and epithelial thickening, and mucus production. These results demonstrate that treatment with a single injection of MSCs reduces the pathophysiological events occurring in an experimental model of allergic asthma by controlling the inflammatory process up to 14 d after transplantation.

摘要

间充质干细胞 (MSC) 研究表明,这些细胞具有调节肺部炎症过程和组织修复的潜力;然而,潜在机制和治疗持久性仍不清楚。在这里,我们研究了人骨髓来源的 MSC 在卵清蛋白诱导的 BALB/c 哮喘小鼠肺部炎症过程和重塑中的治疗潜力,直到移植后 14 天。我们的研究使用卵清蛋白诱导雄性 BALB/c 小鼠发生过敏性哮喘。在哮喘组中通过气管内注射 MSC。收集支气管肺泡灌洗液 (BALF),并进行细胞学检查以测量总蛋白、过氧化氢 (HO) 和促炎 (IL-5、IL-13 和 IL-17A) 和抗炎 (IL-10) 白细胞介素 (IL) 水平。取出肺脏进行组织病理学评估。在第 0 天,哮喘组 BALF 中的嗜酸性粒细胞和淋巴细胞百分比、总蛋白浓度以及 IL-13 和 IL-17A 水平显著增加,证明了过敏性哮喘实验模型的有效性。在第 7 天,MSC 治疗组 BALF 中的嗜酸性粒细胞、淋巴细胞、总蛋白、HO、IL-5、IL-13 和 IL-17A 水平显著降低,而 IL-10 水平显著升高。在第 14 天,MSC 治疗组 BALF 中的总细胞数和淋巴细胞、总蛋白、IL-13 和 IL-17A 水平显著降低。在第 7 天和第 14 天,几乎所有细支气管中的气道重塑都显著减少,表现为炎症浸润、胶原蛋白沉积、肌肉和上皮增厚以及黏液产生减少。这些结果表明,单次注射 MSC 可通过控制移植后 14 天内的炎症过程来减少过敏性哮喘实验模型中的病理生理事件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b86/7444219/a3532aad6fc1/10.1177_0963689720913254-fig1.jpg

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