HO-1-modified umbilical cord MSCs alleviate pulmonary arterial hypertension by reducing inflammation and endothelial dysfunction.

Authors

Riken Chen, Xing Chen, Limei Liang, Huan Li, Liping Xu, Dongjie Huang, Yong Liu, Deyi Zhou, Weilong Ye, Shuyue Zhou, Yihuan Su, Dekang Nie, Zhenzhen Zheng, Yan Deng

Published in

Stem cells translational medicine. Volume 15. Issue 7. May 18, 2026.

Abstract

To evaluate the efficacy of MSCs-HO-1 in pulmonary arterial hypertension (PAH) and explore the underlying mechanisms.
HO-1 expression and localization in lung tissues and vessels were assessed using spatial transcriptomics and single-cell RNA sequencing analyses of human PAH. MSCs-HO-1 were intravenously administered in rat and mouse PAH models (MCT-induced and SuHx). Hemodynamics (RVSP), right ventricular hypertrophy index (RVHI), survival rate, and vascular remodeling were assessed by HE staining and α-SMA immunostaining. Inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-18, IL-10, TGF-β, IL-4, IL-1Ra), ROS levels, and endothelial molecules [nitric oxide (NO) and prostaglandin I2 (PGI2)] were measured. RNA sequencing (RNA-seq) of PAECs was followed by pathway analysis and MAPK validation.
HO-1 was downregulated in PAH patients and models, mainly in the vascular endothelium. MSCs-HO-1 significantly reduced RVSP, RVHI, vascular remodeling, and improved survival compared to unmodified MSCs and HO-1 alone. MSCs-HO-1 inhibited pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-18), increased anti-inflammatory factors (IL-10, TGF-β, IL-4, IL-1Ra), reduced ROS, and restored NO/PGI2. PAEC migration and proliferation abnormalities were corrected. RNA-seq revealed multiple synergistic pathways, with MAPK playing a key role in endothelial protection.
MSCs-HO-1 enhances endothelial function and pulmonary vascular remodeling by modulating antioxidant and immune responses, restoring NO-PGI2 signaling, and suppressing MAPK-mediated inflammation, providing more stable and significant effects than MSCs or HO-1 alone.

PMID:
42367077
Bibliographic data and abstract were imported from PubMed on 29 Jun 2026.

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