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Lung iPSC

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https://www.readbyqxmd.com/read/28456659/n-myc-downstream-regulated-gene-1-ndrg1-promotes-the-stem-like-properties-of-lung-cancer-cells-through-stabilized-c-myc
#1
Yongfang Wang, You Zhou, Feng Tao, Shoujie Chai, Xia Xu, Ying Yang, Yiming Yang, Haiyan Xu, Kai Wang
Tumor-initiating cells (TICs) play an important role in tumorigenesis and development for many various tissue origin cancers including non-small cell lung cancer (NSCLC). However, the mechanism to maintain TICs in NSCLC is still largely unknown. Here, we evaluated differences of mRNA expression between parental and oncosphere cells that enriched TICs. We found that N-myc downstream regulated gene 1(NDRG1) was upregulated in oncosphere cells derived from human NSCLC cell lines and primary NSCLC cells. NDRG1 promoted stem-like properties of LTICs in NSCLC including iPSC (induced pluripotent stem cell) factors (OCT4, SOX2, KLF4, and C-MYC), the spheres-forming ability and the tumorigenicity of NSCLC...
April 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28429504/induced-pluripotent-stem-cells-reduce-neutrophil-chemotaxis-via-activating-grk2-in-endotoxin-induced-acute-lung-injury
#2
Vincent Yi-Fong Su, Shih-Hwa Chiou, Chi-Shiuan Lin, Wei-Chih Chen, Wen-Kuang Yu, Yen-Wen Chen, Cheng-Yu Chen, Kuang-Yao Yang
BACKGROUND AND OBJECTIVE: We investigated the effect of induced pluripotent stem cells (iPSCs) in moderating neutrophil chemotaxis in endotoxin-induced acute lung injury (ALI). METHODS: Male C57BL/6 mice at 8-12 weeks of age were studied. Murine iPSCs were delivered through the tail veins of mice 4 h after intratracheal instillation of endotoxin. Lung histopathological findings, neutrophil counts in peripheral blood and bronchoalveolar lavage fluid (BALF), bone marrow (BM) cell distribution, expression of chemokine receptors and regulatory signalling pathways were analysed after 24 h...
April 21, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28388536/long-noncoding-rna-ror-regulates-chemoresistance-in-docetaxel-resistant-lung-adenocarcinoma-cells-via-epithelial-mesenchymal-transition-pathway
#3
Yan Pan, Jing Chen, Leilei Tao, Kai Zhang, Rui Wang, Xiaoyuan Chu, Longbang Chen
Emerging evidence indicates that the dysregulation of long non-coding RNAs (lncRNAs) contributes to the development and progression of lung adenocarcinoma (LAD), however the underlying mechanism of action of lncRNAs remains unclear. It is well known that the effective treatment of cancers has been hindered by drug resistance in the clinical setting. Epithelial-mesenchymal transition (EMT) has been recognized to be involved in acquiring drug resistance, cell migration and invasion properties in several types of cancer...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28366587/efficient-derivation-of-functional-human-airway-epithelium-from-pluripotent-stem-cells-via-temporal-regulation-of-wnt-signaling
#4
Katherine B McCauley, Finn Hawkins, Maria Serra, Dylan C Thomas, Anjali Jacob, Darrell N Kotton
Effective derivation of functional airway organoids from induced pluripotent stem cells (iPSCs) would provide valuable models of lung disease and facilitate precision therapies for airway disorders such as cystic fibrosis. However, limited understanding of human airway patterning has made this goal challenging. Here, we show that cyclical modulation of the canonical Wnt signaling pathway enables rapid directed differentiation of human iPSCs via an NKX2-1(+) progenitor intermediate into functional proximal airway organoids...
March 22, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28356734/therapeutic-effects-of-proteoliposomes-on-x-linked-chronic-granulomatous-disease-proof-of-concept-using-macrophages-differentiated-from-patient-specific-induced-pluripotent-stem-cells
#5
Julie Brault, Guillaume Vaganay, Aline Le Roy, Jean-Luc Lenormand, Sandra Cortes, Marie José Stasia
Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency due to dysfunction of the phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex leading to severe and recurrent infections in early childhood. The main genetic form is the X-linked CGD leading to the absence of cytochrome b558 composed of NOX2 and p22 (phox) , the membrane partners of the NADPH oxidase complex. The first cause of death of CGD patients is pulmonary infections. Recombinant proteoliposome-based therapy is an emerging and innovative approach for membrane protein delivery, which could be an alternative local, targeted treatment to fight lung infections in CGD patients...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28073160/activation-of-jnk-pathway-aggravates-proteotoxicity-of-hepatic-mutant-z-alpha1-antitrypsin
#6
Nunzia Pastore, Sergio Attanasio, Barbara Granese, Jeffrey Teckman, Andrew A Wilson, Andrea Ballabio, And Nicola Brunetti-Pierri
Alpha1-antitrypsin deficiency is a genetic disease that can affect both the lung and the liver. The vast majority of patients harbor a mutation in the SERPINA1 gene resulting in a single amino acid substitution that results in an unfolded protein that is prone to polymerization. Therefore, the liver disease is caused by a gain of function mechanism due to accumulation of the mutant Z alpha1-antitrypsin (ATZ) and is a key example of an important disease mechanism induced by protein toxicity. Intracellular retention of ATZ triggers a complex injury cascade including apoptosis and other mechanisms, although several aspects of the disease pathogenesis are still unclear...
January 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28057064/the-lncrnas-involved-in-mouse-airway-allergic-inflammation-following-induced-pluripotent-stem-cell-mesenchymal-stem-cell-treatment
#7
Shu-Yue Wang, Xing-Liang Fan, Qiu-Ning Yu, Meng-Xia Deng, Yue-Qi Sun, Wen-Xiang Gao, Cheng-Lin Li, Jian-Bo Shi, Qing-Ling Fu
BACKGROUND: We have previously reported that induced pluripotent stem cell (iPSC)-mesenchymal stem cells (MSCs) alleviated asthma inflammation in mice. Long noncoding RNAs (lncRNAs) were recently reported as being involved in the immune responses. However, whether lncRNAs are associated with iPSC-MSC immunomodulation in allergic inflammation is still unclear. METHODS: Mice were induced into an asthmatic state and received treatment consisting of iPSC-MSCs. Memory T cells isolated from sensitized mice were challenged and co-cultured with iPSC-MSCs in vitro...
January 6, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28000095/exosomes-from-ipscs-delivering-sirna-attenuate-intracellular-adhesion-molecule-1-expression-and-neutrophils-adhesion-in-pulmonary-microvascular-endothelial-cells
#8
Zhihai Ju, Jinhui Ma, Chen Wang, Jie Yu, Yeru Qiao, Feilong Hei
The pro-inflammatory activation of pulmonary microvascular endothelial cells resulting in continuous expression of cellular adhesion molecules, and subsequently recruiting primed neutrophils to form a firm neutrophils-endothelium (PMN-EC) adhesion, has been examined and found to play a vital role in acute lung injury (ALI). RNA interference (RNAi) is a cellular process through harnessing a natural pathway silencing target gene based on recognition and subsequent degradation of specific mRNA sequences. It opens a promising approach for precision medicine...
April 2017: Inflammation
https://www.readbyqxmd.com/read/27895584/induced-pluripotent-stem-cells-inhibit-bleomycin-induced-pulmonary-fibrosis-in-mice-through-suppressing-tgf-%C3%AE-1-smad-mediated-epithelial-to-mesenchymal-transition
#9
Yan Zhou, Zhong He, Yuan Gao, Rui Zheng, Xiaoye Zhang, Li Zhao, Mingqi Tan
Pulmonary fibrosis is a progressive and irreversible fibrotic lung disorder with high mortality and few treatment options. Recently, induced pluripotent stem (iPS) cells have been considered as an ideal resource for stem cell-based therapy. Although, an earlier study demonstrated the therapeutic effect of iPS cells on pulmonary fibrosis, the exact mechanisms remain obscure. The present study investigated the effects of iPS cells on inflammatory responses, transforming growth factor (TGF)-β1 signaling pathway, and epithelial to mesenchymal transition (EMT) during bleomycin (BLM)-induced lung fibrosis...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27779452/induced-pluripotent-stem-cell-model-of-pulmonary-arterial-hypertension-reveals-novel-gene-expression-and-patient-specificity
#10
Silin Sa, Mingxia Gu, James Chappell, Ning-Yi Shao, Mohamed Ameen, Kathryn A T Elliott, Dan Li, Fabian Grubert, Caiyun G Li, Shalina Taylor, Aiqin Cao, Yu Ma, Ryan Fong, Long Nguyen, Joseph C Wu, Michael P Snyder, Marlene Rabinovitch
RATIONALE: Idiopathic or heritable pulmonary arterial hypertension is characterized by loss and obliteration of lung vasculature. Endothelial cell dysfunction is pivotal to the pathophysiology, but different causal mechanisms may reflect a need for patient-tailored therapies. OBJECTIVES: Endothelial cells differentiated from induced pluripotent stem cells were compared with pulmonary arterial endothelial cells from the same patients with idiopathic or heritable pulmonary arterial hypertension, to determine whether they shared functional abnormalities and altered gene expression patterns that differed from those in unused donor cells...
April 1, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27641240/ipsc-derived-mesenchymal-stem-cells-exert-scf-dependent-recovery-of-cigarette-smoke-induced-apoptosis-proliferation-imbalance-in-airway-cells
#11
Xiang Li, Yuelin Zhang, Yingmin Liang, Yuting Cui, Sze C Yeung, Mary S M Ip, Hung-Fat Tse, Qizhou Lian, Judith C W Mak
Mesenchymal stem cells (MSCs) have emerged as a potential cell-based therapy for pulmonary emphysema in animal models. Our previous study demonstrated that human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) were superior over bone marrow-derived MSCs (BM-MSCs) in attenuating cigarette smoke (CS)-induced airspace enlargement possibly through mitochondrial transfer. This study further investigated the effects of iPSC-MSCs on inflammation, apoptosis, and proliferation in a CS-exposed rat model and examined the effects of the secreted paracrine factor from MSCs as another possible mechanism in an in vitro model of bronchial epithelial cells...
February 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27628133/human-pluripotent-stem-cells-ipsc-generation-culture-and-differentiation-to-lung-progenitor-cells
#12
Mahboobe Ghaedi, Laura E Niklason
Induced pluripotent stem (iPS) cells are the product of adult somatic cell reprogramming to an embryonic-like state by inducing a "forced" expression of specific genes. They are similar to natural pluripotent stem cells, such as embryonic stem (ES) cells, in many aspects, such as the expression of certain stem cell genes and potency and differentiability. Human iPS cells are invaluable resource for basic research, cell therapy, drug discovery, and human organ tissue engineering. iPS cells can be derived from the patient to be treated and thus are genetically identical cells that may avoid immune rejection...
September 15, 2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27581487/the-combination-of-crispr-cas9-and-ipsc-technologies-in-the-gene-therapy-of-human-%C3%AE-thalassemia-in-mice
#13
Zhanhui Ou, Xiaohua Niu, Wenyin He, Yuchang Chen, Bing Song, Yexing Xian, Di Fan, Daolin Tang, Xiaofang Sun
β-thalassemia results from point mutations or small deletions in the β-globin (HBB) gene that ultimately cause anemia. The generation of induced pluripotent stem cells (iPSCs) from the somatic cells of patients in combination with subsequent homologous recombination-based gene correction provides new approaches to cure this disease. CRISPR/Cas9 is a genome editing tool that is creating a buzz in the scientific community for treating human diseases, especially genetic disorders. Here, we reported that correction of β-thalassemia mutations in patient-specific iPSCs using the CRISPR/Cas9 tool promotes hematopoietic differentiation in vivo...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27236679/directed-differentiation-of-human-induced-pluripotent-stem-cells-to-mesenchymal-stem-cells
#14
Qizhou Lian, Yuelin Zhang, Xiaoting Liang, Fei Gao, Hung-Fat Tse
Multipotent stromal cells, also known as mesenchymal stem cells (MSCs), possess great potential to generate a wide range of cell types including endothelial cells, smooth muscle cells, bone, cartilage, and lipid cells. This protocol describes in detail how to perform highly efficient, lineage-specific differentiation of human-induced pluripotent stem cells (iPSCs) with an MSCs fate. The approach uses a clinically compliant protocol with chemically defined media, feeder-free conditions, and a CD105 positive and CD24 negative selection to achieve a single cell-based MSCs derivation from differentiating human pluripotent cells in approximately 20 days...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27055225/inhibition-of-src-and-forkhead-box-o1-signaling-by-induced-pluripotent-stem-cell-therapy-attenuates-hyperoxia-augmented-ventilator-induced-diaphragm-dysfunction
#15
Li-Fu Li, Yuh-Lih Chang, Ning-Hung Chen, Chien-Ying Wang, Gwo-Jyh Chang, Meng-Chih Lin, Chih-Hao Chang, Chung-Chi Huang, Jen-Hua Chuang, Yi-Pin Yang, Shih-Hwa Chiou, Yung-Yang Liu
Mechanical ventilation (MV) with hyperoxia is required for providing life support to patients with acute lung injury (ALI). However, MV may cause diaphragm weakness through muscle injury and atrophy, an effect termed ventilator-induced diaphragm dysfunction (VIDD). Src protein tyrosine kinase and class O of forkhead box 1 (FoxO1) mediate acute inflammatory responses and muscle protein degradation induced by oxidative stress. Induced pluripotent stem cells (iPSCs) have been reported to improve hyperoxia-augmented ALI; however, the mechanisms regulating the interactions among VIDD, hyperoxia, and iPSCs are unclear...
July 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27001514/novel-glycylated-sugar-alcohols-protect-esc-specific-micrornas-from-degradation-in-ips-cells
#16
Samantha Chang-Lin, Albert Hung, Donald C Chang, Yi-Wen Lin, Shao-Yao Ying, Shi-Lung Lin
Excessive accumulation of embryonic stem cell (ESC)-specific microRNAs occurs in both ESCs and induced pluripotent stem cells (iPSC); yet, the mechanism involved is unknown. In iPSCs, we for the first time found that novel glycylated sugar alcohols, particularly glycylglycerins, are tightly bound with ESC-specific microRNA precursors (pre-miRNA), such as pre-miR-302. Among these isolated glycylglycerins, we further identified that 1,3-diglycylglycerin and 1,2,3-triglycylglycerin are two major compounds bonded with negatively charged nucleic acids via electro-affinity and subsequently forming sugar-like coats in the hairpin-like double helix structures of pre-miRNAs...
June 2, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/26890744/mir-302-attenuates-amyloid-%C3%AE-induced-neurotoxicity-through-activation-of-akt-signaling
#17
Hsin-Hua Li, Shi-Lung Lin, Chien-Ning Huang, Fung-Jou Lu, Pai-Yi Chiu, Wen-Nung Huang, Te-Jen Lai, Chih-Li Lin
Deficiency of insulin signaling has been linked to diabetes and ageing-related neurodegenerative diseases such as Alzheimer's disease (AD). In this regard, brains exhibit defective insulin receptor substrate-1 (IRS-1) and hence result in alteration of insulin signaling in progression of AD, the most common cause of dementia. Consequently, dysregulation of insulin signaling plays an important role in amyloid-β (Aβ)-induced neurotoxicity. As the derivation of induced pluripotent stem cells (iPSC) involves cell reprogramming, it may provide a means for regaining the control of ageing-associated dysfunction and neurodegeneration via affecting insulin-related signaling...
2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/26840075/therapeutic-benefits-of-induced-pluripotent-stem-cells-in-monocrotaline-induced-pulmonary-arterial-hypertension
#18
Wei-Chun Huang, Meng-Wei Ke, Chin-Chang Cheng, Shih-Hwa Chiou, Shue-Ren Wann, Chih-Wen Shu, Kuan-Rau Chiou, Ching-Jiunn Tseng, Hung-Wei Pan, Guang-Yuan Mar, Chun-Peng Liu
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...
2016: PloS One
https://www.readbyqxmd.com/read/26797607/lung-regeneration-endogenous-and-exogenous-stem-cell-mediated-therapeutic-approaches
#19
REVIEW
Khondoker M Akram, Neil Patel, Monica A Spiteri, Nicholas R Forsyth
The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis...
January 19, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/26753613/directed-dedifferentiation-using-partial-reprogramming-induces-invasive-phenotype-in-melanoma-cells
#20
Nathalie Knappe, Daniel Novak, Kasia Weina, Mathias Bernhardt, Maike Reith, Lionel Larribere, Michael Hölzel, Thomas Tüting, Christoffer Gebhardt, Viktor Umansky, Jochen Utikal
The combination of cancer-focused studies and research related to nuclear reprogramming has gained increasing importance since both processes-reprogramming towards pluripotency and malignant transformation-share essential features. Studies have revealed that incomplete reprogramming of somatic cells leads to malignant transformation indicating that epigenetic regulation associated with iPSC generation can drive cancer development [J Mol Cell Biol 2011;341-350; Cell 2012;151:1617-1632; Cell 2014;156:663-677]...
April 2016: Stem Cells
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