Optimal Dose and Timing of Umbilical Stem Cells Treatment in Pulmonary Arterial Hypertensive Rats.
10.3349/ymj.2017.58.3.570
- Author:
Hyeryon LEE
1
;
Kwan Chang KIM
;
Soo Jin CHOI
;
Young Mi HONG
Author Information
1. Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea. ymhong@ewha.ac.kr
- Publication Type:Original Article
- Keywords:
Pulmonary hypertension;
mesenchymal stem cell;
prophylaxis
- MeSH:
Animals;
Arterial Pressure;
Collagen;
Fetal Blood;
Heart;
Heart Ventricles;
Humans;
Hypertension;
Hypertension, Pulmonary;
Jugular Veins;
Mesenchymal Stromal Cells;
Monocrotaline;
Rats*;
Stem Cells*
- From:Yonsei Medical Journal
2017;58(3):570-580
- CountryRepublic of Korea
- Language:English
-
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. 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. RESULTS: 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. 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.
