Developing PVOD-Specific Therapies

insights from animal models and MSC transplantation

Pulmonary Veno-Occlusive Disease (PVOD), also known as “pulmonary arterial hypertension (PAH), is a rare form of pulmonary hypertension. It is caused by progressive blockage of small veins in the lungs leading to increased pressure followed by right-sided heart failure (1). As effective treatments are limited, lung transplantation remains the only available option. There is no effective medical treatment and lung transplantation is the only curative option. The prognosis is unfavorable, with an average life expectancy of two years following onset of symptoms (2).

Developing PVOD-Specific Therapies

In a recent study researchers investigated the impact of allogeneic mesenchymal stem cell (ASCs) transplantation on lung tissue and its potential in reducing pulmonary hypertension in a rat model of PVOD. Additionally, we assessed whether this intervention contributes to the improvement of right ventricular hypertrophy (3). Continued and future research involving animal models alongside patient samples offers hope for developing PVOD-specific therapies that can prevent and/or treat the disease (4).

Key findings:

• First study to explore the effect of ASC transplantation in an animal model of PVOD.
• Allogeneic ASC transplantation significantly reduced pulmonary microvascular muscularization in the PVOD model.
• Although pulmonary hypertension was not alleviated, right ventricular hypertrophy was notably less severe.
• The double-injection treatment did not prove more effective than a single injection and was associated with increased mortality in the rat models.
• While allogeneic ASC transplantation shows some promise in treating PVOD and associated right ventricular failure, its use should be approached with caution due to potential side effects related to the administration method.

 

NT-proBNP measurements were successfully performed in the PVOD rat model in rat serum utilizing our Rat NT-proBNP ELISA assay.

Rat NT-pro BNP ELISA assay (cat. no. BI-1204R)

• Efficient – only 10 µl / well sample
• Accurate – kit control included – protocol booklet click here
• Reliable – sample values provided –  validation data click here
• Trusted – cited using various rat models – citations click here 

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Rat NT-proBNP ELISA assay

 

Related products:

NT-proANP ELISA Assay (cat. no. BI-20892)

• Small sample volume – 10 µl / well
• Assay suitable for rat and mouse samples – NT-proANP as a cardiovascular safety biomarker in rats Citations

 

Literature:

1. Diagnosis and management of pulmonary veno-occlusive disease. Solinas S, Boucly A, Beurnier A, Kularatne M, Grynblat J, Eyries M, Dorfmüller P, Sitbon O, Humbert M, Montani D. Expert Rev Respir Med. 2023 Jul-Dec;17(8):635-649. doi: 10.1080/17476348.2023.2247989. Epub 2023 Aug 21. PMID: 37578057.
2. Pulmonary Veno-Occlusive Disease. Siddiqui NA, Charoenpong P. 2023 Jul 31. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 36256776.
3. Intravenous mesenchymal stem cell transplantation mitigates pulmonary vascular remodeling but poses dose related risks in a pulmonary veno-occlusive disease model. Katagiri J, Homma J, Takagi R, Sekine H, Shinkawa T, Niinami H, Shimizu T.Stem Cell Res Ther. 2025 May 28;16(1):258. doi: 10.1186/s13287-025-04400-8. PMID: 40437633; PMCID: PMC12121274.
4. Pulmonary veno-occlusive disease: Insights from animal models. Hata A, Gur B, Kalra J, Prabhakar A. Vascul Pharmacol. 2025 Sep 10;161:107547. doi: 10.1016/j.vph.2025.107547. Epub ahead of print. PMID: 40939813.

 

Intravenous mesenchymal stem cell transplantation mitigates pulmonary vascular remodeling but poses dose related risks in a pulmonary veno-occlusive disease model.

Abstract

Background: Pulmonary veno-occlusive disease (PVOD) is a rare subtype of disease that causes pulmonary hypertension with vascular involvement of postcapillary structures of pulmonary vasculature. The disease has a poor prognosis with no effective therapy. The study aimed to determine whether adipose-derived mesenchymal stem cells (ASCs) alleviate pulmonary hypertension and right ventricular hypertrophy in a rat model of PVOD.

Methods: Allogeneic ASCs were intravenously administered to a rat model of PVOD induced by mitomycin C. Then, muscularization in pulmonary microvessels, right ventricular systolic pressure (RVSP), and right ventricular hypertrophy were assessed using immunohistochemistry, right heart catheterization, heart weight, and hematoxylin–eosin (HE) staining. Body weight over time and survival rates were assessed.

Results: ASC transplantation substantially contributed to the reduction of pulmonary microvascular muscularization in the PVOD rat model but not to the decrease in RVSP. Furthermore, it led to the attenuation of right ventricular hypertrophy and a considerable decrease in wall thickness. However, repeated ASC administration increased the mortality rate in the PVOD rat models.

Conclusions: To the best of our knowledge, this is the first study to analyze the effects of ASC transplantation in a rat model of PVOD. While intravenous ASC transplantation exerts beneficial effects on the lungs and right ventricle, adverse events may occur depending on the administration method. Therefore, intravenous ASC transplantation should be performed with caution.