title: Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension.
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.
authors: Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Physical Therapy, Fooyin University, Kaohsiung, Taiwan.
authors: Wei-Chun
authors: WC
authors: Huang
authors: Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors: Meng-Wei
authors: MW
authors: Ke
authors: Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Physical Therapy, Fooyin University, Kaohsiung, Taiwan.
authors: Chin-Chang
authors: CC
authors: Cheng
authors: Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.|Department of Education and Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Shih-Hwa
authors: SH
authors: Chiou
authors: Department of Emergency, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, People's Republic of China.
authors: Shue-Ren
authors: SR
authors: Wann
authors: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors: Chih-Wen
authors: CW
authors: Shu
authors: Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Kuan-Rau
authors: KR
authors: Chiou
authors: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors: Ching-Jiunn
authors: CJ
authors: Tseng
authors: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors: Hung-Wei
authors: HW
authors: Pan
authors: Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors: Guang-Yuan
authors: GY
authors: Mar
authors: Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Chun-Peng
authors: CP
authors: Liu
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D017380:Hypertrophy, Right Ventricular / Q000628:therapy; D007249:Inflammation / Q000235:genetics / Q000628:therapy; D007371:Interferon-gamma / Q000235:genetics; D007378:Interleukins / Q000235:genetics; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D039904:Pluripotent Stem Cells / Q000637:transplantation; D011651:Pulmonary Artery / Q000473:pathology; D051381:Rats
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D007378:Interleukins; D016328:NF-kappa B; D016686:Monocrotaline; D007371:Interferon-gamma