J Korean Med Sci.  2015 May;30(5):576-585. 10.3346/jkms.2015.30.5.576.

The Effect of Umbilical Cord Blood Derived Mesenchymal Stem Cells in Monocrotaline-induced Pulmonary Artery Hypertension Rats

• Lee H
• Lee JC
• Kwon JH
• Kim KC
• Cho MS
• Yang YS
• Oh W
• Choi SJ
• Seo ES
• Lee SJ
• Wang TJ
• Hong YM

• KMID: 2155470
• DOI: http://doi.org/10.3346/jkms.2015.30.5.576

Abstract

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.

Keyword

Hypertension; Pulmonary; Monocrotaline; Cord Blood Stem Cell Transfusion; Gene Expression

MeSH Terms

Animals
Cytokines/metabolism
Disease Models, Animal
Endothelin-1/metabolism
Fetal Blood/*cytology
Gene Expression Regulation/drug effects
Hemodynamics
Humans
Hypertension, Pulmonary/chemically induced/*therapy
Hypertrophy, Right Ventricular/physiopathology
Immunohistochemistry
Lung/metabolism/pathology
Male
Matrix Metalloproteinase 2/metabolism
*Mesenchymal Stem Cell Transplantation
Mesenchymal Stromal Cells/*cytology/metabolism
Monocrotaline/toxicity
Nitric Oxide Synthase Type III/metabolism
Pulmonary Artery/pathology
Rats
Rats, Sprague-Dawley
Receptor, Endothelin A/metabolism
Cytokines
Endothelin-1
Monocrotaline
Matrix Metalloproteinase 2
Nitric Oxide Synthase Type III
Receptor, Endothelin A