The Effect of Umbilical Cord Blood Derived Mesenchymal Stem Cells in Monocrotaline-induced Pulmonary Artery Hypertension Rats.
Pulmonary arterial hypertension (PAH) causes right ventricular failure due to a gradual increase in pulmonary vascular resistance. The purposes of this study were to confirm the engraftment of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) placed in the correct place in the lung and research on changes of hemodynamics, pulmonary pathology, immunomodulation and several gene expressions in monocrotaline (MCT)-induced PAH rat models after hUCB-MSCs transfusion. The rats were grouped as follows: the control (C) group; the M group (MCT 60 mg/kg); the U group (hUCB-MSCs transfusion). They received transfusions via the external jugular vein a week after MCT injection. The mean right ventricular pressure (RVP) was significantly reduced in the U group after the 2 week. The indicators of RV hypertrophy were significantly reduced in the U group at week 4. Reduced medial wall thickness in the pulmonary arteriole was noted in the U group at week 4. Reduced number of intra-acinar muscular pulmonary arteries was observed in the U group after 2 week. Protein expressions such as endothelin (ET)-1, endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase (MMP)-2 significantly decreased at week 4. The decreased levels of ERA, eNOS and MMP-2 immunoreactivity were noted by immnohistochemical staining. After hUCB-MSCs were administered, there were the improvement of RVH and mean RVP. Reductions in several protein expressions and immunomodulation were also detected. It is suggested that hUCB-MSCs may be a promising therapeutic option for PAH.
Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea.
Hyeryon
0000-0002-8566-7503
H
Lee
Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea.
Jae Chul
0000-0002-6539-0922
JC
Lee
Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea.
Jung Hyun
0000-0002-1388-3696
JH
Kwon
Department of Thoracic and Cardiovascular Surgery, Ewha Womans University School of Medicine, Seoul, Korea.
Kwan Chang
0000-0001-8297-5415
KC
Kim
Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea.
Min-Sun
0000-0001-8772-9686
MS
Cho
Biomedical Research Institute, MEDIPOST, Co., Seoul, Korea.
Yoon Sun
0000-0002-5793-6104
YS
Yang
Biomedical Research Institute, MEDIPOST, Co., Seoul, Korea.
Wonil
0000-0002-6349-738X
W
Oh
Biomedical Research Institute, MEDIPOST, Co., Seoul, Korea.
Soo Jin
0000-0002-7885-4212
SJ
Choi
Division of Integrative Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Korea.
Eun-Seok
0000-0003-3465-3846
ES
Seo
Division of Integrative Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Korea.
Sang-Joon
0000-0003-3286-5941
SJ
Lee
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea.
Tae Jun
0000-0002-2870-7046
TJ
Wang
Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea.
Young Mi
0000-0002-6600-7876
YM
Hong
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000628:therapy*; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D016686:Monocrotaline / Q000633:toxicity; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011651:Pulmonary Artery / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism
D016207:Cytokines; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D016686:Monocrotaline; D052250:Nitric Oxide Synthase Type III; D020778:Matrix Metalloproteinase 2
Cord Blood Stem Cell Transfusion; Gene Expression; Hypertension; Monocrotaline; Pulmonary