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

doi:10.1016/j.jconrel.2024.10.056

Surface-engineered mesenchymal stem cell for refractory asthma therapy: Reversing airway remodeling

J Control Release. 2024 Nov 6:376:972-984. doi: 10.1016/j.jconrel.2024.10.056. Online ahead of print.

Authors

Xing-Yue He¹, Meng-Meng Han², Yu-Chen Zhao¹, Ling Tang¹, Yi Wang¹, Lei Xing¹, Ning Wei³, Jing Wang³, Guang-Ji Wang⁴, Fang Zhou⁵, Jee-Heon Jeong⁶, Hu-Lin Jiang⁷

Affiliations

¹ State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
² State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
³ Jiangsu Renocell Biotech Co., Ltd., Nanjing 210009, China.
⁴ Key Laboratory of Drug Metabolism and Pharmacokinetics, Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: [email protected].
⁵ Key Laboratory of Drug Metabolism and Pharmacokinetics, Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: [email protected].
⁶ Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: [email protected].
⁷ State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China; College of Pharmacy, Yanbian University, Yanji 133002, China; Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: [email protected].

PMID: 39476873
DOI: 10.1016/j.jconrel.2024.10.056

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. MSCs/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.

Keywords: Airway remodeling; Angiogenesis; Asthma; Mesenchymal stem cell; Subepithelial fibrosis.