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Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension

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 ro...

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Autores principales: Huang, Wei-Chun, Ke, Meng-Wei, Cheng, Chin-Chang, Chiou, Shih-Hwa, Wann, Shue-Ren, Shu, Chih-Wen, Chiou, Kuan-Rau, Tseng, Ching-Jiunn, Pan, Hung-Wei, Mar, Guang-Yuan, Liu, Chun-Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740504/
https://www.ncbi.nlm.nih.gov/pubmed/26840075
http://dx.doi.org/10.1371/journal.pone.0142476
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author Huang, Wei-Chun
Ke, Meng-Wei
Cheng, Chin-Chang
Chiou, Shih-Hwa
Wann, Shue-Ren
Shu, Chih-Wen
Chiou, Kuan-Rau
Tseng, Ching-Jiunn
Pan, Hung-Wei
Mar, Guang-Yuan
Liu, Chun-Peng
author_facet Huang, Wei-Chun
Ke, Meng-Wei
Cheng, Chin-Chang
Chiou, Shih-Hwa
Wann, Shue-Ren
Shu, Chih-Wen
Chiou, Kuan-Rau
Tseng, Ching-Jiunn
Pan, Hung-Wei
Mar, Guang-Yuan
Liu, Chun-Peng
author_sort Huang, Wei-Chun
collection PubMed
description 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.
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spelling pubmed-47405042016-02-11 Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension Huang, Wei-Chun Ke, Meng-Wei Cheng, Chin-Chang Chiou, Shih-Hwa Wann, Shue-Ren Shu, Chih-Wen Chiou, Kuan-Rau Tseng, Ching-Jiunn Pan, Hung-Wei Mar, Guang-Yuan Liu, Chun-Peng PLoS One Research Article 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. Public Library of Science 2016-02-03 /pmc/articles/PMC4740504/ /pubmed/26840075 http://dx.doi.org/10.1371/journal.pone.0142476 Text en © 2016 Huang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Huang, Wei-Chun
Ke, Meng-Wei
Cheng, Chin-Chang
Chiou, Shih-Hwa
Wann, Shue-Ren
Shu, Chih-Wen
Chiou, Kuan-Rau
Tseng, Ching-Jiunn
Pan, Hung-Wei
Mar, Guang-Yuan
Liu, Chun-Peng
Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension
title Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension
title_full Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension
title_fullStr Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension
title_full_unstemmed Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension
title_short Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension
title_sort therapeutic benefits of induced pluripotent stem cells in monocrotaline-induced pulmonary arterial hypertension
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740504/
https://www.ncbi.nlm.nih.gov/pubmed/26840075
http://dx.doi.org/10.1371/journal.pone.0142476
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