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

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.