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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 - J. Korean Med. Sci. (2015)

Bottom Line: The indicators of RV hypertrophy were significantly reduced in the U group at week 4.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea.

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.

No MeSH data available.


Related in: MedlinePlus

Changes of ET-1, ERA, eNOS, and MMP-2 protein expression levels after hUCB-MSCs injection in PAH rats. These are pictures of protein expression levels of ET-1, ERA, eNOS, and MMP-2 in the lung tissues. The protein expression levels of ET-1, ERA, eNOS, and MMP-2 were significantly increased in the M group compared with the C group at weeks 2 and 4. The protein expression levels of ET-1, ERA, eNOS and MMP-2 were significantly decreased at week 4. *P < 0.05 compared with the C group, †P < 0.05 compared with the M group. C, control group; M, monocrotaline group; U, hUCB-MSCs group.
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Figure 5: Changes of ET-1, ERA, eNOS, and MMP-2 protein expression levels after hUCB-MSCs injection in PAH rats. These are pictures of protein expression levels of ET-1, ERA, eNOS, and MMP-2 in the lung tissues. The protein expression levels of ET-1, ERA, eNOS, and MMP-2 were significantly increased in the M group compared with the C group at weeks 2 and 4. The protein expression levels of ET-1, ERA, eNOS and MMP-2 were significantly decreased at week 4. *P < 0.05 compared with the C group, †P < 0.05 compared with the M group. C, control group; M, monocrotaline group; U, hUCB-MSCs group.

Mentions: The protein expressions of ET-1, ERA, eNOS, and MMP-2 were significantly increased in the M group compared with the C group at weeks 2 and 4. The protein expressions of ET-1, ERA, eNOS, and MMP-2 were significantly decreased in the U group compared with the M group at week 4 (Fig. 5).


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 - J. Korean Med. Sci. (2015)

Changes of ET-1, ERA, eNOS, and MMP-2 protein expression levels after hUCB-MSCs injection in PAH rats. These are pictures of protein expression levels of ET-1, ERA, eNOS, and MMP-2 in the lung tissues. The protein expression levels of ET-1, ERA, eNOS, and MMP-2 were significantly increased in the M group compared with the C group at weeks 2 and 4. The protein expression levels of ET-1, ERA, eNOS and MMP-2 were significantly decreased at week 4. *P < 0.05 compared with the C group, †P < 0.05 compared with the M group. C, control group; M, monocrotaline group; U, hUCB-MSCs group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414641&req=5

Figure 5: Changes of ET-1, ERA, eNOS, and MMP-2 protein expression levels after hUCB-MSCs injection in PAH rats. These are pictures of protein expression levels of ET-1, ERA, eNOS, and MMP-2 in the lung tissues. The protein expression levels of ET-1, ERA, eNOS, and MMP-2 were significantly increased in the M group compared with the C group at weeks 2 and 4. The protein expression levels of ET-1, ERA, eNOS and MMP-2 were significantly decreased at week 4. *P < 0.05 compared with the C group, †P < 0.05 compared with the M group. C, control group; M, monocrotaline group; U, hUCB-MSCs group.
Mentions: The protein expressions of ET-1, ERA, eNOS, and MMP-2 were significantly increased in the M group compared with the C group at weeks 2 and 4. The protein expressions of ET-1, ERA, eNOS, and MMP-2 were significantly decreased in the U group compared with the M group at week 4 (Fig. 5).

Bottom Line: The indicators of RV hypertrophy were significantly reduced in the U group at week 4.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea.

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.

No MeSH data available.


Related in: MedlinePlus