• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

人脐带间充质基质细胞可预防免疫功能正常小鼠肺纤维化的发生。

Mesenchymal stromal cells from human umbilical cord prevent the development of lung fibrosis in immunocompetent mice.

机构信息

Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.

Centro di Tecnologie Avanzate nell'Invecchiamento, IRCCS-INRCA, Ancona, Italy.

出版信息

PLoS One. 2018 Jun 1;13(6):e0196048. doi: 10.1371/journal.pone.0196048. eCollection 2018.

DOI:10.1371/journal.pone.0196048
PMID:29856737
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5983506/
Abstract

Lung fibrosis is a severe condition resulting from several interstial lung diseases (ILD) with different etiologies. Current therapy of ILD, especially those associated with connective tissue diseases, is rather limited and new anti-fibrotic strategies are needed. In this study, we investigated the anti-fibrotic activity in vivo of human mesenchymal stromal cells obtained from whole umbilical cord (hUC-MSC). Adult immunocompetent C57BL/6 mice (n. = 8 for each experimental condition) were injected intravenously with hUC-MSC (n. = 2.5 × 105) twice, 24 hours and 7 days after endotracheal injection of bleomycin. Upon sacrifice at days 8, 14, 21, collagen content, inflammatory cytokine profile, and hUC-MSC presence in explanted lung tissue were analyzed. Systemic administration of a double dose of hUC-MSC significantly reduced bleomycin-induced lung injury (inflammation and fibrosis) in mice through a selective inhibition of the IL6-IL10-TGFβ axis involving lung M2 macrophages. Only few hUC-MSC were detected from explanted lungs, suggesting a "hit and run" mechanism of action of this cellular therapy. Our data indicate that hUC-MSC possess strong in vivo anti-fibrotic activity in a mouse model resembling an immunocompetent human subject affected by inflammatory ILD, providing proof of concept for ad-hoc clinical trials.

摘要

肺纤维化是由多种不同病因的间质性肺病（ILD）引起的严重疾病。ILD 的当前治疗方法，特别是与结缔组织疾病相关的ILD，受到很大限制，需要新的抗纤维化策略。在这项研究中，我们研究了来源于整个脐带的人间充质基质细胞（hUC-MSC）的体内抗纤维化活性。成年免疫功能正常的 C57BL/6 小鼠（每种实验条件下 n = 8）在气管内注射博来霉素后 24 小时和 7 天，两次静脉注射 hUC-MSC（n = 2.5 × 105）。在第 8、14、21 天处死时，分析胶原含量、炎症细胞因子谱和移植肺组织中 hUC-MSC 的存在。两次给予 hUC-MSC 可显著减轻博来霉素诱导的肺损伤（炎症和纤维化），通过选择性抑制涉及肺 M2 巨噬细胞的 IL6-IL10-TGFβ 轴。从移植肺中仅检测到少量 hUC-MSC，提示这种细胞治疗的“打击即跑”作用机制。我们的数据表明，hUC-MSC 在一种类似于受炎症性 ILD 影响的免疫功能正常的人类个体的小鼠模型中具有很强的体内抗纤维化活性，为专门的临床试验提供了概念验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/d1d9a3ab2c04/pone.0196048.g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/b84674114783/pone.0196048.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/33d7c6c0eea6/pone.0196048.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/27cad164b808/pone.0196048.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/1dbd7ea7d2b6/pone.0196048.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/8cac68438eeb/pone.0196048.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/337c29e073ce/pone.0196048.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/166a9f0fb62b/pone.0196048.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/6fa2c0596bcc/pone.0196048.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/9ddafdd12f69/pone.0196048.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/bf159396d660/pone.0196048.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/9bf539123f89/pone.0196048.g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/86cd4ee839db/pone.0196048.g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/d1d9a3ab2c04/pone.0196048.g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/b84674114783/pone.0196048.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/33d7c6c0eea6/pone.0196048.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/27cad164b808/pone.0196048.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/1dbd7ea7d2b6/pone.0196048.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/8cac68438eeb/pone.0196048.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/337c29e073ce/pone.0196048.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/166a9f0fb62b/pone.0196048.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/6fa2c0596bcc/pone.0196048.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/9ddafdd12f69/pone.0196048.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/bf159396d660/pone.0196048.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/9bf539123f89/pone.0196048.g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/86cd4ee839db/pone.0196048.g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd58/5983506/d1d9a3ab2c04/pone.0196048.g013.jpg

相似文献

1
Mesenchymal stromal cells from human umbilical cord prevent the development of lung fibrosis in immunocompetent mice.人脐带间充质基质细胞可预防免疫功能正常小鼠肺纤维化的发生。
PLoS One. 2018 Jun 1;13(6):e0196048. doi: 10.1371/journal.pone.0196048. eCollection 2018.
2
Induction of Mouse Lung Injury by Endotracheal Injection of Bleomycin.通过气管内注射博来霉素诱导小鼠肺损伤。
J Vis Exp. 2019 Apr 30(146). doi: 10.3791/58922.
3
[Therapeutic effects and the underlying mechanism of umbilical cord-derived mesenchymal stem cells for bleomycin induced lung injury in rats].脐带间充质干细胞对博来霉素诱导的大鼠肺损伤的治疗作用及潜在机制
Zhonghua Jie He He Hu Xi Za Zhi. 2013 Nov;36(11):808-13.
4
Role of Keratinocyte Growth Factor in the Differentiation of Sweat Gland-Like Cells From Human Umbilical Cord-Derived Mesenchymal Stem Cells.角质形成细胞生长因子在人脐带间充质干细胞向汗腺样细胞分化中的作用
Stem Cells Transl Med. 2016 Jan;5(1):106-16. doi: 10.5966/sctm.2015-0081. Epub 2015 Nov 16.
5
Human umbilical cord mesenchymal stem cells combined with pirfenidone upregulates the expression of RGS2 in the pulmonary fibrosis in mice.人脐带间充质干细胞联合吡非尼酮上调肺纤维化小鼠中 RGS2 的表达。
Respir Res. 2022 Oct 1;23(1):270. doi: 10.1186/s12931-022-02192-6.
6
Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis.成年肺球状体细胞含有祖细胞，并在博来霉素诱导的肺纤维化啮齿动物中介导再生。
Stem Cells Transl Med. 2015 Nov;4(11):1265-74. doi: 10.5966/sctm.2015-0062. Epub 2015 Sep 10.
7
Extracellular superoxide dismutase increased the therapeutic potential of human mesenchymal stromal cells in radiation pulmonary fibrosis.细胞外超氧化物歧化酶增强了人间充质基质细胞在放射性肺纤维化中的治疗潜力。
Cytotherapy. 2017 May;19(5):586-602. doi: 10.1016/j.jcyt.2017.02.359. Epub 2017 Mar 15.
8
Hepatocyte Growth Factor Is Required for Mesenchymal Stromal Cell Protection Against Bleomycin-Induced Pulmonary Fibrosis.间充质基质细胞保护免受博来霉素诱导的肺纤维化需要肝细胞生长因子。
Stem Cells Transl Med. 2016 Oct;5(10):1307-1318. doi: 10.5966/sctm.2015-0337. Epub 2016 Jul 7.
9
Attenuating Effect of Long-term Culture of Umbilical Cord Vein Mesenchymal Stromal Cells on Pulmonary Fibrosis in C57BL/6 Mice.脐静脉间充质基质细胞长期培养对C57BL/6小鼠肺纤维化的减轻作用
Iran J Allergy Asthma Immunol. 2017 Dec;16(6):501-510.
10
Human adipose mesenchymal stem cells as potent anti-fibrosis therapy for systemic sclerosis.人脂肪间充质干细胞作为全身性硬皮病的有效抗纤维化治疗方法。
J Autoimmun. 2016 Jun;70:31-9. doi: 10.1016/j.jaut.2016.03.013. Epub 2016 Apr 1.

引用本文的文献

1
Pirfenidone combined with UC-MSCs reversed bleomycin-induced pulmonary fibrosis.吡非尼酮联合脐带间充质干细胞可逆转博来霉素诱导的肺纤维化。
Sci Rep. 2025 Aug 4;15(1):28339. doi: 10.1038/s41598-025-14286-4.
2
Adoptive Transfer of T Cells as a Potential Therapeutic Approach in the Bleomycin-Injured Mouse Lung.过继转移T细胞作为博来霉素损伤小鼠肺的一种潜在治疗方法。
J Gene Med. 2025 Apr;27(4):e70018. doi: 10.1002/jgm.70018.
3
Preclinical Evaluation of the Safety, Toxicity and Efficacy of Genetically Modified Wharton's Jelly Mesenchymal Stem/Stromal Cells Expressing the Antimicrobial Peptide SE-33.

本文引用的文献

1
Comparative analysis of human Wharton's jelly mesenchymal stem cells derived from different parts of the same umbilical cord.比较分析同一脐带不同部位来源的人脐带华通氏胶间充质干细胞。
Cell Tissue Res. 2018 Apr;372(1):51-65. doi: 10.1007/s00441-017-2699-4. Epub 2017 Dec 4.
2
Overexpression of OSM and IL-6 impacts the polarization of pro-fibrotic macrophages and the development of bleomycin-induced lung fibrosis.OSM 和 IL-6 的过表达影响促纤维化巨噬细胞的极化和博来霉素诱导的肺纤维化的发展。
Sci Rep. 2017 Oct 16;7(1):13281. doi: 10.1038/s41598-017-13511-z.
3
Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span.
表达抗菌肽SE-33的基因编辑脐带华通氏胶间充质干/基质细胞的安全性、毒性及有效性的临床前评估
Cells. 2025 Feb 26;14(5):341. doi: 10.3390/cells14050341.
4
Immunopathological characteristics and therapeutic effects of UC-MSCs in a pigeon breeder's lung mouse model.脐带来源间充质干细胞在鸽饲养者肺小鼠模型中的免疫病理特征及治疗效果
Acta Biochim Biophys Sin (Shanghai). 2025 Jan 21;57(3):473-485. doi: 10.3724/abbs.2025010.
5
Human Umbilical Cord-Mesenchymal Stem Cells Combined With Low Dosage Nintedanib Rather Than Using Alone Mitigates Pulmonary Fibrosis in Mice.人脐带间充质干细胞联合低剂量尼达尼布而非单独使用可减轻小鼠肺纤维化。
Stem Cells Int. 2025 Jan 7;2025:9445735. doi: 10.1155/sci/9445735. eCollection 2025.
6
A systematic review and meta-analysis of clinical trials assessing safety and efficacy of human extracellular vesicle-based therapy.一项系统评价和荟萃分析临床试验评估基于人细胞外囊泡治疗的安全性和有效性。
J Extracell Vesicles. 2024 Jul;13(7):e12458. doi: 10.1002/jev2.12458.
7
Stem cell-based therapy for fibrotic diseases: mechanisms and pathways.基于干细胞的纤维化疾病治疗：机制与途径。
Stem Cell Res Ther. 2024 Jun 18;15(1):170. doi: 10.1186/s13287-024-03782-5.
8
Antler stem cell exosomes alleviate pulmonary fibrosis via inhibiting recruitment of monocyte macrophage, rather than polarization of M2 macrophages in mice.鹿茸干细胞外泌体通过抑制单核巨噬细胞的募集而非小鼠M2巨噬细胞的极化来减轻肺纤维化。
Cell Death Discov. 2023 Sep 28;9(1):359. doi: 10.1038/s41420-023-01659-9.
9
Progress in research on mesenchymal stem cells and their extracellular vesicles for treating fibrosis in systemic sclerosis.间充质干细胞及其细胞外囊泡治疗系统性硬化症纤维化的研究进展
Clin Exp Med. 2023 Nov;23(7):2997-3009. doi: 10.1007/s10238-023-01136-8. Epub 2023 Jul 17.
10
Reversal of Pulmonary Fibrosis: Human Umbilical Mesenchymal Stem Cells from Wharton's Jelly versus Human-Adipose-Derived Mesenchymal Stem Cells.肺纤维化的逆转：人脐带华通氏胶间充质干细胞与人体脂肪来源间充质干细胞的比较。
Int J Mol Sci. 2023 Apr 8;24(8):6948. doi: 10.3390/ijms24086948.
单核细胞来源的肺泡巨噬细胞驱动肺纤维化，并在整个生命周期中持续存在于肺中。
J Exp Med. 2017 Aug 7;214(8):2387-2404. doi: 10.1084/jem.20162152. Epub 2017 Jul 10.
4
Clinical observation of umbilical cord mesenchymal stem cell treatment of severe idiopathic pulmonary fibrosis: A case report.脐带间充质干细胞治疗重度特发性肺纤维化的临床观察：一例报告
Exp Ther Med. 2017 May;13(5):1922-1926. doi: 10.3892/etm.2017.4222. Epub 2017 Mar 10.
5
Update of EULAR recommendations for the treatment of systemic sclerosis.EULAR 系统性硬皮病治疗推荐更新。
Ann Rheum Dis. 2017 Aug;76(8):1327-1339. doi: 10.1136/annrheumdis-2016-209909. Epub 2016 Nov 9.
6
Human Adipose-derived Mesenchymal Stem Cells Attenuate Early Stage of Bleomycin Induced Pulmonary Fibrosis: Comparison with Pirfenidone.人脂肪间充质干细胞减轻博来霉素诱导的早期肺纤维化：与吡非尼酮的比较。
Int J Stem Cells. 2016 Nov 30;9(2):192-206. doi: 10.15283/ijsc16041.
7
Inflammaging and 'Garb-aging'.炎症与“垃圾-衰老”。
Trends Endocrinol Metab. 2017 Mar;28(3):199-212. doi: 10.1016/j.tem.2016.09.005. Epub 2016 Oct 24.
8
Biodistribution and Clearance of Human Mesenchymal Stem Cells by Quantitative Three-Dimensional Cryo-Imaging After Intravenous Infusion in a Rat Lung Injury Model.大鼠肺损伤模型静脉输注后人骨髓间充质干细胞的生物分布及通过定量三维冷冻成像的清除情况
Stem Cells Transl Med. 2016 Dec;5(12):1668-1675. doi: 10.5966/sctm.2015-0379. Epub 2016 Jul 26.
9
Mesenchymal stromal cells from the foreskin: Tissue isolation, cell characterization and immunobiological properties.来自包皮的间充质基质细胞：组织分离、细胞表征及免疫生物学特性
Cytotherapy. 2016 Mar;18(3):320-35. doi: 10.1016/j.jcyt.2015.11.013.
10
Inflammation, fibrosis, and modulation of the process by mesenchymal stem/stromal cells.炎症、纤维化以及间充质干/基质细胞对该过程的调节。
Matrix Biol. 2016 Apr;51:7-13. doi: 10.1016/j.matbio.2016.01.010. Epub 2016 Jan 22.