Optimal Dose and Timing of Umbilical Stem Cells Treatment in Pulmonary Arterial Hypertensive Rats

Abstract

Purpose: Pulmonary arterial hypertension (PAH) is a fatal disease which is characterized by an increase in pulmonary arterial pressure leading to increases in right ventricular afterload. Human umbilical cord blood derived-mesenchymal stem cells (hUCB-MSCs) administered via the jugular vein have been previously shown to improve PAH by reversal treatment. However, the effect of low dosage and transfusion timing of hUCB-MSCs on PAH has not yet been clearly established. Obviously, low dosage treatment can lead to a reduction in costs. This is the first study on early transfusion effect. Materials and Methods: This study was divided into two parts. The first part is an investigation of dose-dependent effect. hUCBMSCs were administered into 3 groups of rats (UA: 3x10(6) cells, UB: 1.5x10(6) cells, UC: 3x10(5) cells) via the external jugular vein at week 1 after monocrotaline (MCT) injection. The second part is a search for optimal treatment timing in 3x10(5) cells dose of hUCBMSCs administered at day 1 for UD group (low dose of hUCB-MSCs at day 1), at day 1 and week 1 for the UE group (dual transfusion of low dose of hUCB-MSCs at day 1 and week 1) and at 1 week for the UF group (reversal treatment of low dose hUCB-MSC at week 1) after MCT injection. Results: The administration of 3x10(5) hUCB-MSCs was as effective as the 3x10(6) dose in decreasing mean right ventricle (RV) pressure and pulmonary pathological changes. Early treatment with hUCB-MSCs improved mean RV pressure, pulmonary pathological changes and heart collagen 3 protein expression levels in PAH. Conclusion: Low-dose early treatment of hUCB-MSCs is as effective as a high dose treatment of hUCB-MSCs in improving PAH although dual or reversal treatment is still more effective.