表层工程间充质干细胞用于难治性哮喘的治疗：逆转气道重塑
2024/11/29
摘要
在哮喘的发展过程中，上皮下纤维化和血管增生引起气道重塑和狭窄，导致疾病恶化和呼吸衰竭。在临床上，哮喘的治疗旨在通过吸入性皮质类固醇（ICS）降低哮喘急性发作的频率。然而，由于气道重塑主要由上皮下纤维化和气管腔周围血管生成形成，ICS不能阻止其向难治性哮喘的进展。在此，我们通过将间充质干细胞与负载vactosertib （VST）和linifanib （LFN）的活性氧响应性聚合物胶束生物偶联，构建了表面工程间充质干细胞（MSCs/PVLA），通过逆转气道重塑来治疗难治性哮喘。MSC/PVLA在炎症趋向性作用下迁移至气管腔内，释放VST和LFN，通过抑制上皮下纤维化和血管生成，抑制气道重塑的形成。同时，MSC减少炎性细胞浸润和细胞因子分泌，调节病理微环境。我们的研究结果表明，MSC/PVLA可能是一个有希望的候选药物，以预防疾病恶化和治疗难治性哮喘。
Surface-engineered mesenchymal stem cell for refractory asthma therapy: Reversing airway remodeling
Xing-Yue He, Meng-Meng Han, Yu-Chen Zhao, Ling Tang, Yi Wang, Lei Xing, Ning Wei, Jing Wang, Guang-Ji Wang, Fang Zhou, Jee-Heon Jeong, Hu-Lin Jiang
Abstract
In the development of asthma, subepithelial fibrosis and vascular proliferation cause airway remodeling and narrowing, leading to disease deterioration and respiratory failure. In the clinic, the treatment of asthma was aimed at reducing the frequency of acute asthma attacks through inhaled corticosteroids (ICSs). However, ICSs cannot prevent the progression into refractory asthma due to the formation of airway remodeling mainly by subepithelial fibrosis and angiogenesis surrounding the tracheal lumen. Herein, we constructed surface-engineered mesenchymal stem cells (MSCs/PVLA) via the bioconjugation of MSCs and reactive oxygen species-responsive polymeric micelles loaded with vactosertib (VST) and linifanib (LFN) for treating refractory asthma through reversing airway remodeling. MSC/PVLA migrated to the tracheal lumen due to the inflammation tropism of MSCs, and subsequently released VST and LFN could inhibit the formation of airway remodeling by preventing subepithelial fibrosis and angiogenesis. Meanwhile, MSCs reduced inflammatory cell infiltration and cytokine secretion to regulate the pathological microenvironment. Our results suggested that MSCs/PVLA could serve as a promising candidate to prevent disease exacerbations and treat refractory asthma.
在哮喘的发展过程中，上皮下纤维化和血管增生引起气道重塑和狭窄，导致疾病恶化和呼吸衰竭。在临床上，哮喘的治疗旨在通过吸入性皮质类固醇（ICS）降低哮喘急性发作的频率。然而，由于气道重塑主要由上皮下纤维化和气管腔周围血管生成形成，ICS不能阻止其向难治性哮喘的进展。在此，我们通过将间充质干细胞与负载vactosertib （VST）和linifanib （LFN）的活性氧响应性聚合物胶束生物偶联，构建了表面工程间充质干细胞（MSCs/PVLA），通过逆转气道重塑来治疗难治性哮喘。MSC/PVLA在炎症趋向性作用下迁移至气管腔内，释放VST和LFN，通过抑制上皮下纤维化和血管生成，抑制气道重塑的形成。同时，MSC减少炎性细胞浸润和细胞因子分泌，调节病理微环境。我们的研究结果表明，MSC/PVLA可能是一个有希望的候选药物，以预防疾病恶化和治疗难治性哮喘。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Control Release. 2024 Oct 28:S0168-3659(24)00729-6. doi: 10.1016/j.jconrel.2024.10.056.)
(J Control Release. 2024 Oct 28:S0168-3659(24)00729-6. doi: 10.1016/j.jconrel.2024.10.056.)
Surface-engineered mesenchymal stem cell for refractory asthma therapy: Reversing airway remodeling
Xing-Yue He, Meng-Meng Han, Yu-Chen Zhao, Ling Tang, Yi Wang, Lei Xing, Ning Wei, Jing Wang, Guang-Ji Wang, Fang Zhou, Jee-Heon Jeong, Hu-Lin Jiang
Abstract
In the development of asthma, subepithelial fibrosis and vascular proliferation cause airway remodeling and narrowing, leading to disease deterioration and respiratory failure. In the clinic, the treatment of asthma was aimed at reducing the frequency of acute asthma attacks through inhaled corticosteroids (ICSs). However, ICSs cannot prevent the progression into refractory asthma due to the formation of airway remodeling mainly by subepithelial fibrosis and angiogenesis surrounding the tracheal lumen. Herein, we constructed surface-engineered mesenchymal stem cells (MSCs/PVLA) via the bioconjugation of MSCs and reactive oxygen species-responsive polymeric micelles loaded with vactosertib (VST) and linifanib (LFN) for treating refractory asthma through reversing airway remodeling. MSC/PVLA migrated to the tracheal lumen due to the inflammation tropism of MSCs, and subsequently released VST and LFN could inhibit the formation of airway remodeling by preventing subepithelial fibrosis and angiogenesis. Meanwhile, MSCs reduced inflammatory cell infiltration and cytokine secretion to regulate the pathological microenvironment. Our results suggested that MSCs/PVLA could serve as a promising candidate to prevent disease exacerbations and treat refractory asthma.
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