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


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.


CONCLUSIONS
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.
Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea.
Hyeryon
H
Lee
Department of Thoracic and Cardiovascular Surgery, Ewha Womans University School of Medicine, Seoul, Korea.
Kwan Chang
KC
Kim
Biomedical Research Institute, MEDIPOST, Co., Seoul, Korea.
Soo Jin
SJ
Choi
Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea. ymhong@ewha.ac.kr.
Young Mi
YM
Hong
D000818:Animals; D004195:Disease Models, Animal; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000628:therapy*; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D016686:Monocrotaline / Q000633:toxicity; D011651:Pulmonary Artery / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016686:Monocrotaline
Pulmonary hypertension; mesenchymal stem cell; prophylaxis