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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

Human UCB-MSCs preparation. Characterization of hUCB-MSCs at passage 5. hUCB-MSCs by phase-contrast microscopy (A). Cells grow uniformly and have a spindle-shape (left). PKH26-labeled MSCs are stained in red (middle, × 200). Immunophenotype from UCB-hMSCs (B). These cells are positive for antigens CD73, CD90 and CD105 but generally not for antigens HLA-DR, CD34 and CD45. The gray lines indicate the isotype matched mouse IgG antibody control labeling.
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Figure 1: Human UCB-MSCs preparation. Characterization of hUCB-MSCs at passage 5. hUCB-MSCs by phase-contrast microscopy (A). Cells grow uniformly and have a spindle-shape (left). PKH26-labeled MSCs are stained in red (middle, × 200). Immunophenotype from UCB-hMSCs (B). These cells are positive for antigens CD73, CD90 and CD105 but generally not for antigens HLA-DR, CD34 and CD45. The gray lines indicate the isotype matched mouse IgG antibody control labeling.

Mentions: We found that hUCB-MSCs grew uniformly. They appeared to be spindle-shaped (left). PKH26-labeled hUCB-MSCs were stained in red (middle). We did not observe any trypan blue positive cells (red: PKH26, blue: trypan blue) (Fig. 1A). The cells were positive for the cell surface markers CD73, CD90, and CD105, but negative for the hematopoietic cell-specific surface markers CD34, CD45, as well as for the MHC class II marker HLA-DR. The gray lines indicate the isotype matched the mouse Ig G antibody control labeling (Fig. 1B). We were able to identify hUCB-MSCs at passage 5 with a CD73+, CD90+, CD105+, CD34-, CD45-, and HLA-DR. hUCB-MSCs did not express hematopoietic markers; CD45+, CD34+, CD105-, CD73-, CD90-. Characterization of hUCB-MSCs by flow cytometry was performed in a cultured cells.


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)

Human UCB-MSCs preparation. Characterization of hUCB-MSCs at passage 5. hUCB-MSCs by phase-contrast microscopy (A). Cells grow uniformly and have a spindle-shape (left). PKH26-labeled MSCs are stained in red (middle, × 200). Immunophenotype from UCB-hMSCs (B). These cells are positive for antigens CD73, CD90 and CD105 but generally not for antigens HLA-DR, CD34 and CD45. The gray lines indicate the isotype matched mouse IgG antibody control labeling.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Human UCB-MSCs preparation. Characterization of hUCB-MSCs at passage 5. hUCB-MSCs by phase-contrast microscopy (A). Cells grow uniformly and have a spindle-shape (left). PKH26-labeled MSCs are stained in red (middle, × 200). Immunophenotype from UCB-hMSCs (B). These cells are positive for antigens CD73, CD90 and CD105 but generally not for antigens HLA-DR, CD34 and CD45. The gray lines indicate the isotype matched mouse IgG antibody control labeling.
Mentions: We found that hUCB-MSCs grew uniformly. They appeared to be spindle-shaped (left). PKH26-labeled hUCB-MSCs were stained in red (middle). We did not observe any trypan blue positive cells (red: PKH26, blue: trypan blue) (Fig. 1A). The cells were positive for the cell surface markers CD73, CD90, and CD105, but negative for the hematopoietic cell-specific surface markers CD34, CD45, as well as for the MHC class II marker HLA-DR. The gray lines indicate the isotype matched the mouse Ig G antibody control labeling (Fig. 1B). We were able to identify hUCB-MSCs at passage 5 with a CD73+, CD90+, CD105+, CD34-, CD45-, and HLA-DR. hUCB-MSCs did not express hematopoietic markers; CD45+, CD34+, CD105-, CD73-, CD90-. Characterization of hUCB-MSCs by flow cytometry was performed in a cultured cells.

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