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Lung iPSC

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...
September 19, 2016: Journal of Cellular and Molecular Medicine
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
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
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
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
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
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
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
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...
2016: International Journal of Molecular Sciences
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
Chen Wang, Feilong Hei, Zhihai Ju, Jie Yu, Shengnan Yang, Mengmeng Chen
Human alveolar type II (AT II) epithelial cells are valuable for the cellular therapy of lung disease. Human induced pluripotent stem cells (iPSCs) have the ability to generate AT II cells that can be used in modeling and treatment of lung disease caused by dysfunction of AT II cells. In this study, we present a simple, effective, and noninvasive way of obtaining human iPSCs from exfoliated renal epithelial cells, which exist in urine. Alkaline phosphatase (AP) staining, immunofluorescence staining, karyotyping, and teratoma experiments have proved that these iPSCs are pluripotent...
February 2016: Cellular Reprogramming
Shahd Horie, Claire Masterson, James Devaney, John G Laffey
PURPOSE OF REVIEW: Acute respiratory distress syndrome (ARDS) is a devastating disease process with a 40% mortality rate, and for which there is no therapy. Stem cells are an exciting potential therapy for ARDS, and are currently the subject of intensive ongoing research efforts. We review data concerning the therapeutic promise of cell-based therapies for ARDS. RECENT FINDINGS: Recent experimental studies suggest that cell-based therapies, particularly mesenchymal stem/stromal cells (MSCs), endothelial progenitor cells, and embryonic or induced pluripotent stem cells all offer considerable promise for ARDS...
February 2016: Current Opinion in Critical Care
Chorng-Kuang How, Sen-Kuang Hou, Luen-Kui Chen, Cheng-Ming Yang, Hsien-Hao Huang, Hsin-Chin Shih, Mu-Shun Huang, Shih-Hwa Chiou, Chen-Hsen Lee, Chi-Chang Juan
BACKGROUND: Mesenteric ischemia-reperfusion (I/R) injury is a serious pathophysiologic process that can trigger the development of multiorgan dysfunction. Acute lung injury is a major cause of death among mesenteric I/R patients, as current treatments remain inadequate. Stem cell-based therapies are considered novel strategies for treating several devastating and incurable diseases. This study examined whether induced pluripotent stem cells (iPSCs) lacking c-myc (i.e., induced using only the three genes oct4, sox2, and klf4) can protect against acute lung injury in a mesenteric I/R mouse model...
October 2015: Journal of Trauma and Acute Care Surgery
Erin A Kimbrel, Robert Lanza
Pluripotent stem cells (PSCs) hold great promise for drug discovery and regenerative medicine owing to their ability to differentiate into any cell type in the body. After more than three decades of research, including delays due to the potential tumorigenicity of PSCs and inefficiencies in differentiation methods, the field is at a turning point, with a number of clinical trials across the globe now testing PSC-derived products in humans. Ocular diseases dominate these first-in-man trials, and Phase l/ll results are showing promising safety data as well as possible efficacy...
October 2015: Nature Reviews. Drug Discovery
Amy L Firth, Tushar Menon, Gregory S Parker, Susan J Qualls, Benjamin M Lewis, Eugene Ke, Carl T Dargitz, Rebecca Wright, Ajai Khanna, Fred H Gage, Inder M Verma
Lung disease is a major cause of death in the United States, with current therapeutic approaches serving only to manage symptoms. The most common chronic and life-threatening genetic disease of the lung is cystic fibrosis (CF) caused by mutations in the cystic fibrosis transmembrane regulator (CFTR). We have generated induced pluripotent stem cells (iPSCs) from CF patients carrying a homozygous deletion of F508 in the CFTR gene, which results in defective processing of CFTR to the cell membrane. This mutation was precisely corrected using CRISPR to target corrective sequences to the endogenous CFTR genomic locus, in combination with a completely excisable selection system, which significantly improved the efficiency of this correction...
September 1, 2015: Cell Reports
Der-Cherng Tarng, Wei-Cheng Tseng, Pei-Ying Lee, Shih-Hwa Chiou, Shie-Liang Hsieh
Teratoma-like formation addresses a critical safety concern for the potential utility of induced pluripotent stem cells (iPSCs). Therefore, therapy utilizing iPSC-derived conditioned medium (iPSC-CM) for acute kidney injury (AKI) has attracted substantial interest. A recent study showed that iPSC-CM effectively alleviated ventilator-induced lung injury in rats. It prompts us to assess the therapeutic effects of iPSC-CM on ischemic AKI. First, we assessed the changes in renal function and tubular cell apoptosis by intraperitoneal administration of iPSC-CM to ischemia-reperfusion (I/R) rats...
2016: Cell Transplantation
Collin T Stabler, Shimon Lecht, Philip Lazarovici, Peter I Lelkes
INTRODUCTION: Mesenchymal stem cells (MSCs) of different biological sources are in Phase 1 clinical trials and are being considered for Phase 2 therapy of lung disorders, and lung (progenitor) cells derived from pluripotent stem cells (SCs) are under development in preclinical animal models. SOURCES OF DATA: and AREAS OF AGREEMENT: There is consensus about the therapeutic potential of transplanted SCs, mainly MSCs, primarily involves paracrine 'bystander' effects that confer protection of the epithelial and endothelial linings of the lung caused by inflammation and/or fibrosis and lead to increased survival in animal models...
September 2015: British Medical Bulletin
Mahboobe Ghaedi, Laura E Niklason, Jordana Williams
Considerable progress has been made in the field of in vitro development of alveolar epithelium from induced pluripotent stem cells. Patient specific derived alveolar cells could potentially populate tissue engineered lungs, provide a cell source for drug testing or function as a model for research into lung diseases. Induced to pluripotency through a variety of techniques, stem cells can be differentiated to alveolar epithelium through exposure to a variety of different culture conditions and growth media...
March 1, 2015: Current Transplantation Reports
Sebastian V Rojas, Andreas Martens, Robert Zweigerdt, Hassina Baraki, Christian Rathert, Natalie Schecker, Sara Rojas-Hernandez, Kristin Schwanke, Ulrich Martin, Axel Haverich, Ingo Kutschka
OBJECTIVES: The aim of this study was to investigate whether a fibrinogen biomatrix improves the transplantation effectiveness of induced pluripotent stem cells (iPSCs) in a model of myocardial infarction. BACKGROUND: Early retention, engraftment, and cell proliferation are important factors for successful cardiac stem cell therapy. Common transplantation techniques involve the direction injection of cells in aqueous media. However, this approach yields low retention and variable cell biodistribution, leading to reduced grafts that are unable to sufficiently regenerate damaged myocardium...
July 2015: Tissue Engineering. Part A
Finn Hawkins, Darrell N Kotton
The discovery of embryonic and induced pluripotent stem cells (ESCs and iPSCs) has ushered in an exciting new era of regenerative medicine. Human pluripotent stem cells can be "directed" in vitro toward lung epithelium by applying specific stepwise combinations of growth factors that recapitulate the molecular mechanisms of respiratory development in animal models. In a relatively short time, there has been significant progress in deriving lung epithelium from ESCs/iPSCs. These directed differentiation protocols include high concentrations of activin A to induce definitive endoderm followed by dual inhibition of bone morphogenic protein and TGF-β signaling pathways to produce anterior foregut endoderm...
March 2015: Annals of the American Thoracic Society
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