Katagiri Junko, Homma Jun, Takagi Ryo, Sekine Hidekazu, Shinkawa Takeshi, Niinami Hiroshi, Shimizu Tatsuya
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, TWIns, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Department of Cardiovascular Surgery, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Stem Cell Res Ther. 2025 May 28;16(1):258. doi: 10.1186/s13287-025-04400-8.
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.
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.
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.
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.
肺静脉闭塞病（PVOD）是一种罕见的疾病亚型，可导致肺动脉高压，并累及肺血管后毛细血管结构。该疾病预后较差，尚无有效治疗方法。本研究旨在确定脂肪来源的间充质干细胞（ASCs）是否能减轻PVOD大鼠模型中的肺动脉高压和右心室肥厚。
将同种异体ASCs静脉注射到丝裂霉素C诱导的PVOD大鼠模型中。然后，使用免疫组织化学、右心导管检查、心脏重量和苏木精-伊红（HE）染色评估肺微血管肌化、右心室收缩压（RVSP）和右心室肥厚情况。评估随时间变化的体重和生存率。
ASC移植对PVOD大鼠模型中肺微血管肌化的减少有显著作用，但对RVSP的降低无作用。此外，它导致右心室肥厚减轻，壁厚显著降低。然而，重复给予ASCs会增加PVOD大鼠模型的死亡率。
据我们所知，这是第一项分析ASC移植在PVOD大鼠模型中作用的研究。虽然静脉注射ASC移植对肺和右心室有有益作用，但根据给药方法可能会出现不良事件。因此，静脉注射ASC移植应谨慎进行。
