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Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension
- Source :
- PLoS ONE, PLoS ONE, Vol 11, Iss 2, p e0142476 (2016)
- Publication Year :
- 2016
- Publisher :
- Public Library of Science (PLoS), 2016.
-
Abstract
- Pulmonary arterial hypertension (PAH) is characterized by progressive increases in vascular resistance and the remodeling of pulmonary arteries. The accumulation of inflammatory cells in the lung and elevated levels of inflammatory cytokines in the bloodstream suggest that inflammation may play a role in PAH. In this study, the benefits of induced pluripotent stem cells (iPSCs) and iPSC-conditioned medium (iPSC CM) were explored in monocrotaline (MCT)-induced PAH rats. We demonstrated that both iPSCs and iPSC CM significantly reduced the right ventricular systolic pressure and ameliorated the hypertrophy of the right ventricle in MCT-induced PAH rats in models of both disease prevention and disease reversal. In the prevention of MCT-induced PAH, iPSC-based therapy led to the decreased accumulation of inflammatory cells and down-regulated the expression of the IL-1β, IL-6, IL-12α, IL-12β, IL-23 and IFNγ genes in lung specimens, which implied that iPSC-based therapy may be involved in the regulation of inflammation. NF-κB signaling is essential to the inflammatory cascade, which is activated via the phosphorylation of the NF-κB molecule. Using the chemical inhibitor specifically blocked the phosphorylation of NF-κB, and in vitro assays of cultured human M1 macrophages implied that the anti-inflammation effect of iPSC-based therapy may contribute to the disturbance of NF-κB activation. Here, we showed that iPSC-based therapy could restore the hemodynamic function of right ventricle with benefits for preventing the ongoing inflammation in the lungs of MCT-induced PAH rats by regulating NF-κB phosphorylation.
- Subjects :
- Male
0301 basic medicine
Pathology
medicine.medical_treatment
lcsh:Medicine
Artificial Gene Amplification and Extension
030204 cardiovascular system & hematology
Pharmacology
Pathology and Laboratory Medicine
Biochemistry
Polymerase Chain Reaction
Muscle hypertrophy
White Blood Cells
0302 clinical medicine
Animal Cells
Medicine and Health Sciences
Phosphorylation
Post-Translational Modification
Enzyme-Linked Immunoassays
Pulmonary Arteries
lcsh:Science
Induced pluripotent stem cell
Lung
Immune Response
Cells, Cultured
Monocrotaline
Multidisciplinary
Stem Cells
Stem Cell Therapy
NF-kappa B
Arteries
Stem-cell therapy
medicine.anatomical_structure
Cytokines
Cellular Types
Anatomy
medicine.symptom
Research Article
Adult
Pluripotent Stem Cells
medicine.medical_specialty
Hypertension, Pulmonary
Immune Cells
Immunology
Induced Pluripotent Stem Cells
Down-Regulation
Inflammation
Pulmonary Artery
Biology
Research and Analysis Methods
Proinflammatory cytokine
Interferon-gamma
03 medical and health sciences
Signs and Symptoms
medicine.artery
medicine
Animals
Humans
Immunoassays
Molecular Biology Techniques
Molecular Biology
Clinical Genetics
Blood Cells
Hypertrophy, Right Ventricular
Interleukins
Macrophages
lcsh:R
Biology and Life Sciences
Proteins
Cell Biology
Reverse Transcriptase-Polymerase Chain Reaction
medicine.disease
Pulmonary hypertension
Rats
Disease Models, Animal
030104 developmental biology
Culture Media, Conditioned
Pulmonary artery
Immunologic Techniques
Cardiovascular Anatomy
Blood Vessels
lcsh:Q
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....94f0bb7bd256130c5447d78e7b8b52e7