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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

Inflammatory cytokine expressions in the lung tissues. To screen whether hUCB-MSCs affected local production of inflammatory cytokines by lung cells in three groups, a cytokine array was performed on lung homogenates (A) CINC-1, ICAM-1, LIX, LECAM-1, CXCL7, and VEGF were higher in the M group, whereas CINC-1, ICAM-1, LIX, LECAM-1, CXCL7, and VEGF were lower in the U group compared to the M group. CINC-2a/b, CX3CL1, and TIMP-1 were not different in three groups (B). White bars, control (n = 6); gray bars, monocrotaline (n = 6); black bars, hUCB-MSCs (n = 7). CINC-1, cytokine-induced neutrophil chemoattractant-1; CINC-2a/b, cytokine-induced neutrophil chemoattractant-2a/b; CX3CL1, chemokine (C-X-C motif) ligand 1; ICAM, inter-cellular adhesion molecule; LIX, lipopolysaccharide-induced CXC chemokine; LECAM-1, leukocyte endothelial cell adhesion molecule 1; CXCL7, chemokine (C-X-C motif) ligand 7; TIMP-1, tissue inhibitor of metalloproteinase 1; VEGF, vascular endothelial growth factor. *P < 0.05 compared with the C group, †P < 0.05 compared with the M group. C, control; M, monocrotaline; U, hUCB-MSCs.
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Figure 6: Inflammatory cytokine expressions in the lung tissues. To screen whether hUCB-MSCs affected local production of inflammatory cytokines by lung cells in three groups, a cytokine array was performed on lung homogenates (A) CINC-1, ICAM-1, LIX, LECAM-1, CXCL7, and VEGF were higher in the M group, whereas CINC-1, ICAM-1, LIX, LECAM-1, CXCL7, and VEGF were lower in the U group compared to the M group. CINC-2a/b, CX3CL1, and TIMP-1 were not different in three groups (B). White bars, control (n = 6); gray bars, monocrotaline (n = 6); black bars, hUCB-MSCs (n = 7). CINC-1, cytokine-induced neutrophil chemoattractant-1; CINC-2a/b, cytokine-induced neutrophil chemoattractant-2a/b; CX3CL1, chemokine (C-X-C motif) ligand 1; ICAM, inter-cellular adhesion molecule; LIX, lipopolysaccharide-induced CXC chemokine; LECAM-1, leukocyte endothelial cell adhesion molecule 1; CXCL7, chemokine (C-X-C motif) ligand 7; TIMP-1, tissue inhibitor of metalloproteinase 1; VEGF, vascular endothelial growth factor. *P < 0.05 compared with the C group, †P < 0.05 compared with the M group. C, control; M, monocrotaline; U, hUCB-MSCs.

Mentions: To screen whether hUCB-MSCs affected local production of inflammatory cytokines to many kinds of cells in the lung tissues in three groups, a cytokine array was performed on lung homogenates (Fig. 6A). Nine inflammatory cytokines such as cytokine-induced neutrophil chemoattractant-1 (CINC-1); cytokine-induced neutrophil chemoattractant-2a/b (CINC-2a/b); chemokine (C-X-C motif) ligand 1 (CX3CL1); inter-cellular adhesion molecule 1 (ICAM-1); lipopolysaccharide-induced CXC chemokine (LIX); leukocyte endothelial cell adhesion molecule 1 (LECAM-1); chemokine (C-X-C motif) ligand 7 (CXCL7); tissue inhibitor of metalloproteinase 1 (TIMP-1) and vascular endothelial growth factor (VE-GF) were performed in three groups. CINC-1, ICAM-1, LIX, LECAM-1, CXCL7, and VEGF were higher in the M group, whereas CINC-1, ICAM-1, LIX, LECAM-1, CXCL7, and VEGF were lower in the U group compared to the M group. CINC-2a/b, CX3CL1, and TIMP-1 were not different in three groups (Fig. 6B).


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)

Inflammatory cytokine expressions in the lung tissues. To screen whether hUCB-MSCs affected local production of inflammatory cytokines by lung cells in three groups, a cytokine array was performed on lung homogenates (A) CINC-1, ICAM-1, LIX, LECAM-1, CXCL7, and VEGF were higher in the M group, whereas CINC-1, ICAM-1, LIX, LECAM-1, CXCL7, and VEGF were lower in the U group compared to the M group. CINC-2a/b, CX3CL1, and TIMP-1 were not different in three groups (B). White bars, control (n = 6); gray bars, monocrotaline (n = 6); black bars, hUCB-MSCs (n = 7). CINC-1, cytokine-induced neutrophil chemoattractant-1; CINC-2a/b, cytokine-induced neutrophil chemoattractant-2a/b; CX3CL1, chemokine (C-X-C motif) ligand 1; ICAM, inter-cellular adhesion molecule; LIX, lipopolysaccharide-induced CXC chemokine; LECAM-1, leukocyte endothelial cell adhesion molecule 1; CXCL7, chemokine (C-X-C motif) ligand 7; TIMP-1, tissue inhibitor of metalloproteinase 1; VEGF, vascular endothelial growth factor. *P < 0.05 compared with the C group, †P < 0.05 compared with the M group. C, control; M, monocrotaline; U, hUCB-MSCs.
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Figure 6: Inflammatory cytokine expressions in the lung tissues. To screen whether hUCB-MSCs affected local production of inflammatory cytokines by lung cells in three groups, a cytokine array was performed on lung homogenates (A) CINC-1, ICAM-1, LIX, LECAM-1, CXCL7, and VEGF were higher in the M group, whereas CINC-1, ICAM-1, LIX, LECAM-1, CXCL7, and VEGF were lower in the U group compared to the M group. CINC-2a/b, CX3CL1, and TIMP-1 were not different in three groups (B). White bars, control (n = 6); gray bars, monocrotaline (n = 6); black bars, hUCB-MSCs (n = 7). CINC-1, cytokine-induced neutrophil chemoattractant-1; CINC-2a/b, cytokine-induced neutrophil chemoattractant-2a/b; CX3CL1, chemokine (C-X-C motif) ligand 1; ICAM, inter-cellular adhesion molecule; LIX, lipopolysaccharide-induced CXC chemokine; LECAM-1, leukocyte endothelial cell adhesion molecule 1; CXCL7, chemokine (C-X-C motif) ligand 7; TIMP-1, tissue inhibitor of metalloproteinase 1; VEGF, vascular endothelial growth factor. *P < 0.05 compared with the C group, †P < 0.05 compared with the M group. C, control; M, monocrotaline; U, hUCB-MSCs.
Mentions: To screen whether hUCB-MSCs affected local production of inflammatory cytokines to many kinds of cells in the lung tissues in three groups, a cytokine array was performed on lung homogenates (Fig. 6A). Nine inflammatory cytokines such as cytokine-induced neutrophil chemoattractant-1 (CINC-1); cytokine-induced neutrophil chemoattractant-2a/b (CINC-2a/b); chemokine (C-X-C motif) ligand 1 (CX3CL1); inter-cellular adhesion molecule 1 (ICAM-1); lipopolysaccharide-induced CXC chemokine (LIX); leukocyte endothelial cell adhesion molecule 1 (LECAM-1); chemokine (C-X-C motif) ligand 7 (CXCL7); tissue inhibitor of metalloproteinase 1 (TIMP-1) and vascular endothelial growth factor (VE-GF) were performed in three groups. CINC-1, ICAM-1, LIX, LECAM-1, CXCL7, and VEGF were higher in the M group, whereas CINC-1, ICAM-1, LIX, LECAM-1, CXCL7, and VEGF were lower in the U group compared to the M group. CINC-2a/b, CX3CL1, and TIMP-1 were not different in three groups (Fig. 6B).

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