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

• Published in: Yonsei medical journal 2017, 58(3), , pp.570-580
• Main Authors: Lee, Hyeryon, Kim, Kwan Chang, Choi, Soo Jin, Hong, Young Mi
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary - chemically induced; Hypertension, Pulmonary - therapy; Hypertrophy, Right Ventricular - physiopathology; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Monocrotaline - toxicity; Original; Pulmonary Artery - pathology; Rats; Rats, Sprague-Dawley; Time Factors; 의학일반
• ISSN: 0513-5796; 1976-2437
• DOI: 10.3349/ymj.2017.58.3.570

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. This study was divided into two parts. The first part is an investigation of dose-dependent effect. hUCB-MSCs were administered into 3 groups of rats (UA: 3×10⁶ cells, UB: 1.5×10⁶ cells, UC: 3×10⁵ cells) via the external jugular vein at week 1 after monocrotaline (MCT) injection. The second part is a search for optimal treatment timing in 3×10⁵ cells dose of hUCB-MSCs 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. The administration of 3×10⁵ hUCB-MSCs was as effective as the 3×10⁶ 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. 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.