Tracheal delivery of HO-1-modified human umbilical cord-derived mesenchymal stem cells treats pulmonary arterial hypertension by enhancing pulmonary antioxidant and anti-inflammatory responses.

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Pulmonary arterial hypertension (PAH) is a life-threatening cardiovascular disease, with current treatments only alleviating symptoms. Mesenchymal stem cells (MSCs) possess immune-regulatory and reparative properties, and HO-1-modified MSCs enhance their anti-inflammatory and antioxidant effects. This study aims to investigate the potential of tracheal delivery of HO-1-modified MSCs for the treatment of PAH. This study first assessed the levels of inflammation and oxidative stress in the lung tissue pathology of healthy donors and IPAH patients, detecting F4/80, IL-6, and the oxidative stress marker 8-OHdG. Subsequently, in MCT-induced rat and hypoxia-exposed mouse models, we evaluated lung tissue sections for HE staining and α-SMA immunohistochemistry, along with antioxidant enzymes (SOD, CAT, GSH) and inflammatory factors (TNF-α, IL-18, IL-6, IL-1β) at 1, 2, 3, 4, and 5 weeks to assess the effects of various treatments. Next, we compared the anti-inflammatory and antioxidant capacities of HO-1-modified MSCs derived from umbilical cord (UC-MSCs) and adipose tissue (AD-MSCs), selecting the best cell intervention strategy. Using in vivo imaging, we assessed the cell homing of intravenously injected cells and drug retention after tracheal delivery. After tracheal delivery of HO-1-MSCs at 3, 4, and 5 weeks, we analyzed IHC staining for α-SMA, right heart catheterization, lung tiss

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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