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Lung iPSC

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https://www.readbyqxmd.com/read/29652170/pulmonary-transplantation-of-human-ipsc-derived-macrophages-ameliorates-pulmonary-alveolar-proteinosis
#1
Christine Happle, Nico Lachmann, Mania Ackermann, Anja Mirenska, Gudrun Göhring, Kathrin Thomay, Adele Mucci, Miriam Hetzel, Torsten Glomb, Takuji Suzuki, Claudia Chalk, Silke Glage, Oliver Dittrich-Breiholz, Bruce Trapnell, Thomas Moritz, Gesine Hansen
Rationale While the transplantation of induced pluripotent stem cell (iPSC)-derived cells harbors enormous potential for the treatment of pulmonary diseases, in vivo data demonstrating clear therapeutic benefits of human iPSC-derived cells in lung disease models is missing. Objective We here tested the therapeutic potential of iPSC-derived macrophages in a humanized disease model of hereditary pulmonary alveolar proteinosis (herPAP). herPAP is caused by a genetic defect of the GM-CSF-receptor, which leads to disturbed macrophage differentiation and protein/surfactant degradation in the lungs subsequently resulting in severe respiratory insufficiency...
April 13, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29621663/up-regulation-of-pi-3-kinases-and-the-activation-of-pi3k-akt-signaling-pathway-in-cancer-stem-like-cells-through-dna-hypomethylation-mediated-by-the-cancer-microenvironment
#2
Aung Ko Ko Oo, Anna Sanchez Calle, Neha Nair, Hafizah Mahmud, Arun Vaidyanath, Junya Yamauchi, Aprilliana Cahya Khayrani, Juan Du, Md Jahangir Alam, Akimasa Seno, Akifumi Mizutani, Hiroshi Murakami, Yoshiaki Iwasaki, Ling Chen, Tomonari Kasai, Masaharu Seno
Previously, we have succeeded in converting induced pluripotent stem cells (iPSCs) into cancer stem cells (CSCs) by treating the iPSCs with conditioned medium of Lewis lung carcinoma (LLC) cells. The converted CSCs, named miPS-LLCcm cells, exhibited the self-renewal, differentiation potential, and potential to form malignant tumors with metastasis. In this study, we further characterized miPS-LLCcm cells both in vivo and in vitro. The tumors formed by subcutaneous injection showed the structures with pathophysiological features consisting of undifferentiated and malignant phenotypes generally found in adenocarcinoma...
April 2, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29576613/hoxb7-overexpression-in-lung-cancer-is-a-hallmark-of-acquired-stem-like-phenotype
#3
Simona Monterisi, Pietro Lo Riso, Karin Russo, Giovanni Bertalot, Manuela Vecchi, Giuseppe Testa, Pier Paolo Di Fiore, Fabrizio Bianchi
HOXB7 is a homeodomain (HOX) transcription factor involved in regional body patterning of invertebrates and vertebrates. We previously identified HOXB7 within a ten-gene prognostic signature for lung adenocarcinoma, where increased expression of HOXB7 was associated with poor prognosis. This raises the question of how HOXB7 overexpression can influence the metastatic behavior of lung adenocarcinoma. Here, we analyzed publicly available microarray and RNA-seq lung cancer expression datasets and found that HOXB7-overexpressing tumors are enriched in gene signatures characterizing adult and embryonic stem cells (SC), and induced pluripotent stem cells (iPSC)...
March 26, 2018: Oncogene
https://www.readbyqxmd.com/read/29523190/differentiation-of-human-induced-pluripotent-stem-cells-into-nucleus-pulposus-like-cells
#4
Ruhang Tang, Liufang Jing, Vincent P Willard, Chia-Lung Wu, Farshid Guilak, Jun Chen, Lori A Setton
BACKGROUND: Intervertebral disc (IVD) degeneration is characterized by an early decrease in cellularity of the nucleus pulposus (NP) region, and associated extracellular matrix changes, reduced hydration, and progressive degeneration. Cell-based IVD therapy has emerged as an area of great interest, with studies reporting regenerative potential for many cell sources, including autologous or allogeneic chondrocytes, primary IVD cells, and stem cells. Few approaches, however, have clear strategies to promote the NP phenotype, in part due to a limited knowledge of the defined markers and differentiation protocols for this lineage...
March 9, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29435942/identification-and-isolation-of-novel-sugar-like-rna-protecting-materials-glycylglycerins-from-pluripotent-stem-cells
#5
Shi-Lung Lin
Pluripotent stem cells are a resourceful treasure box for regenerative medicine. They contain a large variety of novel materials useful for designing and developing new medicines and therapies directed against many aging-associated degenerative disorders, including Alzheimer's disease, Parkinson's disease, stroke, diabetes, osteoporosis, and cancers. Currently, identification of these novel stem cell-specific materials is one of major breakthroughs in the field of stem cell research. Particularly, since the discovery of induced pluripotent stem cells (iPSC) in year 2006, the methods of iPSC derivation further provide an unlimited resource for screening, isolating, and even producing theses novel stem cell-specific materials in vitro...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29435941/the-mir-302-mediated-induction-of-pluripotent-stem-cells-ipsc-multiple-synergistic-reprogramming-mechanisms
#6
Shao-Yao Ying, William Fang, Shi-Lung Lin
Pluripotency represents a unique feature of embryonic stem cells (ESCs). To generate ESC-like-induced pluripotent stem cells (iPSCs) derived from somatic cells, the cell genome needs to be reset and reprogrammed to express the ESC-specific transcriptome. Numerous studies have shown that genomic DNA demethylation is required for epigenetic reprogramming of somatic cell nuclei to form iPSCs; yet, the mechanism remains largely unclear. In ESCs, the reprogramming process goes through two critical stages: germline and zygotic demethylation, both of which erase genomic DNA methylation sites and hence allow for different gene expression patterns to be reset into a pluripotent state...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29435940/mechanism-and-method-for-generating-tumor-free-ips-cells-using-intronic-microrna-mir-302-induction
#7
Shi-Lung Lin, Shao-Yao Ying
Today's researchers generating induced pluripotent stem cells (iPS cells or iPSCs) usually consider their pluripotency rather than potential tumorigenicity. Oncogenic factors such as c-Myc and Klf4 are frequently used to boost the survival and proliferative rates of iPSCs, creating an inevitable problem of tumorigenicity that hinders the therapeutic usefulness of these iPSCs. To prevent stem cell tumorigenicity, we have examined mechanisms by which the cell cycle genes are regulated in embryonic stem cells (ESCs)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29435919/the-microrna
#8
Shao-Yao Ying, Donald C Chang, Shi-Lung Lin
MicroRNAs (miRNAs), widely distributed, small regulatory RNA genes, target both messenger RNA (mRNA) degradation and suppression of protein translation based on sequence complementarity between the miRNA and its targeted mRNA. Different names have been used to describe various types of miRNA. During evolution, RNA retroviruses or transgenes invaded the eukaryotic genome and were inserted itself in the noncoding regions of DNA, conceivably acting as transposon-like jumping genes, providing defense from viral invasion and fine-tuning of gene expression as a secondary level of gene modulation in eukaryotes...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29298421/primary-cilium-mediated-retinal-pigment-epithelium-maturation-is-disrupted-in-ciliopathy-patient-cells
#9
Helen Louise May-Simera, Qin Wan, Balendu Shekhar Jha, Juliet Hartford, Vladimir Khristov, Roba Dejene, Justin Chang, Sarita Patnaik, Quanlong Lu, Poulomi Banerjee, Jason Silver, Christine Insinna-Kettenhofen, Dishita Patel, Mostafa Lotfi, May Malicdan, Nathan Hotaling, Arvydas Maminishkis, Rupa Sridharan, Brian Brooks, Kiyoharu Miyagishima, Meral Gunay-Aygun, Rajarshi Pal, Christopher Westlake, Sheldon Miller, Ruchi Sharma, Kapil Bharti
Primary cilia are sensory organelles that protrude from the cell membrane. Defects in the primary cilium cause ciliopathy disorders, with retinal degeneration as a prominent phenotype. Here, we demonstrate that the retinal pigment epithelium (RPE), essential for photoreceptor development and function, requires a functional primary cilium for complete maturation and that RPE maturation defects in ciliopathies precede photoreceptor degeneration. Pharmacologically enhanced ciliogenesis in wild-type induced pluripotent stem cells (iPSC)-RPE leads to fully mature and functional cells...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29285401/multifunctional-stimuli-responsive-polymer-gated-iron-and-gold-embedded-silica-nano-golf-balls-nanoshuttles-for-targeted-on-demand-theranostics
#10
Liping Wang, Grace Jang, Deependra Kumar Ban, Vrinda Sant, Jay Seth, Sami Kazmi, Nirav Patel, Qingqing Yang, Joon Lee, Woraphong Janetanakit, Shanshan Wang, Brian P Head, Gennadi Glinsky, Ratneshwar Lal
Multi-functional nanoshuttles for remotely targeted and on-demand delivery of therapeutic molecules and imaging to defined tissues and organs hold great potentials in personalized medicine, including precise early diagnosis, efficient prevention and therapy without toxicity. Yet, in spite of 25 years of research, there are still no such shuttles available. To this end, we have designed magnetic and gold nanoparticles (NP)-embedded silica nanoshuttles (MGNSs) with nanopores on their surface. Fluorescently labeled Doxorubicin (DOX), a cancer drug, was loaded in the MGNSs as a payload...
2017: Bone Research
https://www.readbyqxmd.com/read/29226550/alpha-klotho-enrichment-in-induced-pluripotent-stem-cell-secretome-contributes-to-antioxidative-protection-in-acute-lung-injury
#11
Amiq Gazdhar, Priya Ravikumar, Johanne Pastor, Manfred Heller, Jianfeng Ye, Jianning Zhang, Orson W Moe, Thomas Geiser, Connie C W Hsia
Induced pluripotent stem cells (iPSCs) have been reported to alleviate organ injury, although the mechanisms of action remain unclear and administration of intact cells faces many limitations. We hypothesized that cell-free conditioned media (CM) containing the secretome of iPSCs possess antioxidative constituents that can alleviate pulmonary oxidant stress damage. We derived iPSCs from human dermal fibroblasts and harvested the CM. Addition of iPSC CM to cultured human alveolar type-1 epithelial cells mitigated hyperoxia-induced depletion of endogenous total antioxidant capacity while tracheal instillation of iPSC CM into adult rat lungs enhanced hyperoxia-induced increase in TAC...
December 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/29216777/the-long-and-winding-road-stem-cells-for-cystic-fibrosis
#12
Massimo Conese, Elisa Beccia, Stefano Castellani, Sante Di Gioia, Carla Colombo, Antonella Angiolillo, Annalucia Carbone
Cystic fibrosis (CF) is a genetic syndrome with a high mortality rate due to severe lung disease. Despite having several drugs targeting specific mutated CFTR proteins already in clinical trials, new therapies, based on stem cells, are also emerging to treat those patients. Areas covered: The authors review the main sources of stem cells, including embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs), gestational stem cells, and adult stem cells, such as mesenchymal stem cells (MSCs) in the context of CF...
March 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29123113/talen-mediated-functional-correction-of-human-ipsc-derived-macrophages-in-context-of-hereditary-pulmonary-alveolar-proteinosis
#13
Alexandra Kuhn, Mania Ackermann, Claudio Mussolino, Toni Cathomen, Nico Lachmann, Thomas Moritz
Hereditary pulmonary alveolar proteinosis (herPAP) constitutes a rare, life threatening lung disease characterized by the inability of alveolar macrophages to clear the alveolar airspaces from surfactant phospholipids. On a molecular level, the disorder is defined by a defect in the CSF2RA gene coding for the GM-CSF receptor alpha-chain (CD116). As therapeutic options are limited, we currently pursue a cell and gene therapy approach aiming for the intrapulmonary transplantation of gene-corrected macrophages derived from herPAP-specific induced pluripotent stem cells (herPAP-iPSC) employing transcriptional activator-like effector nucleases (TALENs)...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115383/induced-pluripotent-stem-cell-conditioned-medium-suppresses-pulmonary-fibroblast-to-myofibroblast-differentiation-via-the-inhibition-of-tgf-%C3%AE-1-smad-pathway
#14
Yan Zhou, Qiang Zhang, Yuan Gao, Mingqi Tan, Rui Zheng, Li Zhao, Xiaoye Zhang
Therapeutic strategies based on stem cells have been shown to have potential in improving the condition of severe lung diseases. In this study, the suppressive effects of conditioned medium (CM) of induced pluripotent stem cells (iPSCs) on pulmonary fibroblast differentiation were investigated in a series of in vitro and in vivo experiments. Moreover, the underlying mechanisms through which iPSC-CM inhibited the differentiation of fibroblasts into myofibroblasts were explored as well. iPSCs were generated using a mouse 3-gene transfection method, myofibroblast-like cells were induced by incubating human fibroblasts with transforming growth factor-β1 (TGF-β1) and mouse models of pulmonary fibrosis (PF) were established by an injection of bleomycin...
January 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29056548/human-induced-pluripotent-stem-cell-derived-lung-progenitor-and-alveolar-epithelial-cells-attenuate-hyperoxia-induced-lung-injury
#15
Mehdi Shafa, Lavinia Iuliana Ionescu, Arul Vadivel, Jennifer J P Collins, Liqun Xu, Shumei Zhong, Martin Kang, Geneviève de Caen, Manijeh Daneshmand, Jenny Shi, Katherine Z Fu, Andrew Qi, Ying Wang, James Ellis, William L Stanford, Bernard Thébaud
BACKGROUND AIMS: Bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by disrupted lung growth, is the most common complication in extreme premature infants. BPD leads to persistent pulmonary disease later in life. Alveolar epithelial type 2 cells (AEC2s), a subset of which represent distal lung progenitor cells (LPCs), promote normal lung growth and repair. AEC2 depletion may contribute to persistent lung injury in BPD. We hypothesized that induced pluripotent stem cell (iPSC)-derived AECs prevent lung damage in experimental oxygen-induced BPD...
January 2018: Cytotherapy
https://www.readbyqxmd.com/read/29024475/bioengineered-lungs-generated-from-human-ipscs-derived-epithelial-cells-on-native-extracellular-matrix
#16
Mahboobe Ghaedi, Andrew V Le, Go Hatachi, Arkadi Beloiartsev, Kevin Rocco, Amogh Sivarapatna, Julio J Mendez, Pavlina Baevova, Rachel N Dyal, Katie L Leiby, Eric S White, Laura E Niklason
The development of an alternative source for donor lungs would change the paradigm of lung transplantation. Recent studies have demonstrated the potential feasibility of using decellularized lungs as scaffolds for lung tissue regeneration and subsequent implantation. However, finding a reliable cell source and the ability to scale up for recellularization of the lung scaffold still remain significant challenges. To explore the possibility of regeneration of human lung tissue from stem cells in vitro, populations of lung progenitor cells were generated from human iPSCs...
March 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28987320/lung-development-regeneration-and-plasticity-from-disease-physiopathology-to-drug-design-using-induced-pluripotent-stem-cells
#17
REVIEW
Engi Ahmed, Caroline Sansac, Said Assou, Delphine Gras, Aurélie Petit, Isabelle Vachier, Pascal Chanez, John De Vos, Arnaud Bourdin
Lungs have a complex structure composed of different cell types that form approximately 17 million airway branches of gas-delivering bronchioles connected to 500 million gas-exchanging alveoli. Airways and alveoli are lined by epithelial cells that display a low rate of turnover at steady-state, but can regenerate the epithelium in response to injuries. Here, we review the key points of lung development, homeostasis and epithelial cell plasticity in response to injury and disease, because this knowledge is required to develop new lung disease treatments...
March 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28935813/asxl3-is-a-novel-pluripotency-factor-in-human-respiratory-epithelial-cells-and-a-potential-therapeutic-target-in-small-cell-lung-cancer
#18
Vivek Shukla, Mahadev Rao, Hongen Zhang, Jeanette Beers, Darawalee Wangsa, Danny Wangsa, Floryne O Buishand, Yonghong Wang, Zhiya Yu, Holly S Stevenson, Emily S Reardon, Kaitlin C McLoughlin, Andrew S Kaufman, Eden C Payabyab, Julie A Hong, Mary Zhang, Sean Davis, Daniel Edelman, Guokai Chen, Markku M Miettinen, Nicholas P Restifo, Thomas Ried, Paul A Meltzer, David S Schrump
In this study, we generated induced pluripotent stem cells (iPSC) from normal human small airway epithelial cells (SAEC) to investigate epigenetic mechanisms of stemness and pluripotency in lung cancers. We documented key hallmarks of reprogramming in lung iPSCs (Lu-iPSC) that coincided with modulation of more than 15,000 genes relative to parental SAECs. Of particular novelty, we identified the PRC2-associated protein, ASXL3, which was markedly upregulated in Lu-iPSCs and small cell lung cancer (SCLC) lines and clinical specimens...
November 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28922348/stem-cell-biology-and-regenerative-medicine-for-neonatal-lung-diseases
#19
REVIEW
Martin Kang, Bernard Thébaud
Lung diseases remain one of the main causes of morbidity and mortality in neonates. Cell therapy and regenerative medicine have the potential to revolutionize the management of life-threatening and debilitating lung diseases that currently lack effective treatments. Over the past decade, the repair capabilities of stem/progenitor cells have been harnessed to prevent/rescue lung damage in experimental neonatal lung diseases. Mesenchymal stromal cells and amnion epithelial cells exert pleiotropic effects and represent ideal therapeutic cells for bronchopulmonary dysplasia, a multifactorial disease...
January 2018: Pediatric Research
https://www.readbyqxmd.com/read/28911970/mesenchymal-stem-cells-alleviate-oxidative-stress-induced-mitochondrial-dysfunction-in-the-airways
#20
Xiang Li, Charalambos Michaeloudes, Yuelin Zhang, Coen H Wiegman, Ian M Adcock, Qizhou Lian, Judith C W Mak, Pankaj K Bhavsar, Kian Fan Chung
BACKGROUND: Oxidative stress-induced mitochondrial dysfunction can contribute to inflammation and remodeling in patients with chronic obstructive pulmonary disease (COPD). Mesenchymal stem cells protect against lung damage in animal models of COPD. It is unknown whether these effects occur through attenuating mitochondrial dysfunction in airway cells. OBJECTIVE: We sought to examine the effect of induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) on oxidative stress-induce mitochondrial dysfunction in human airway smooth muscle cells (ASMCs) in vitro and in mouse lungs in vivo...
September 11, 2017: Journal of Allergy and Clinical Immunology
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