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Stem cell pulmonary fibrosis

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https://www.readbyqxmd.com/read/28191779/development-of-a-three-dimensional-bioengineering-technology-to-generate-lung-tissue-for-personalized-disease-modeling
#1
Dan C Wilkinson, Jackelyn A Alva-Ornelas, Jennifer M S Sucre, Preethi Vijayaraj, Abdo Durra, Wade Richardson, Steven J Jonas, Manash K Paul, Saravanan Karumbayaram, Bruce Dunn, Brigitte N Gomperts
Stem cell technologies, especially patient-specific, induced stem cell pluripotency and directed differentiation, hold great promise for changing the landscape of medical therapies. Proper exploitation of these methods may lead to personalized organ transplants, but to regenerate organs, it is necessary to develop methods for assembling differentiated cells into functional, organ-level tissues. The generation of three-dimensional human tissue models also holds potential for medical advances in disease modeling, as full organ functionality may not be necessary to recapitulate disease pathophysiology...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28157203/hepatocyte-growth-factor-secreted-by-bone-marrow-stem-cell-reduce-er-stress-and-improves-repair-in-alveolar-epithelial-ii-cells
#2
Izabela Nita, Katrin Hostettler, Luca Tamo, Michaela Medová, Giuseppe Bombaci, Jun Zhong, Ramanjaneyulu Allam, Yitzhak Zimmer, Michael Roth, Thomas Geiser, Amiq Gazdhar
Idiopathic Pulmonary Fibrosis (IPF) is a progressive, irreversible lung disease with complex pathophysiology. Evidence of endoplasmic reticulum (ER) stress has been reported in alveolar epithelial cells (AEC) in IPF patients. Secreted mediators from bone marrow stem cells (BMSC-cm) have regenerative properties. In this study we investigate the beneficial effects of BMSC-cm on ER stress response in primary AEC and ER stressed A549 cells. We hypothesize that BMSC-cm reduces ER stress. Primary AEC isolated from IPF patients were treated with BMSC-cm...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28138398/comparative-analysis-of-morphological-and-molecular-motifs-in-bronchiolitis-obliterans-and-alveolar-fibroelastosis-after-lung-and-stem-cell-transplantation
#3
Danny Jonigk, Berenice Rath, Paul Borchert, Peter Braubach, Lavinia Maegel, Nicole Izykowski, Gregor Warnecke, Wiebke Sommer, Hans Kreipe, Robert Blach, Adrian Anklamm, Axel Haverich, Matthias Eder, Michael Stadler, Tobias Welte, Jens Gottlieb, Mark Kuehnel, Florian Laenger
Chronic lung allograft dysfunction (CLAD) remains the major obstacle to long-term survival following lung transplantation (LuTx). Morphologically CLAD is defined by obliterative remodelling of the small airways (bronchiolitis obliterans, BO) as well as a more recently described collagenous obliteration of alveoli with elastosis summarised as alveolar fibroelastosis (AFE). Both patterns are not restricted to pulmonary allografts, but have also been reported following haematopoietic stem cell transplantation (HSCT) and radio chemotherapy (RC)...
January 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28098218/the-role-of-mir-497-5p-in-myofibroblast-differentiation-of-lr-mscs-and-pulmonary-fibrogenesis
#4
Xiang Chen, Chaowen Shi, Cong Wang, Weilin Liu, Yanhong Chu, Zou Xiang, Kebin Hu, Ping Dong, Xiaodong Han
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal fibrotic lung disease characterized by profound changes in stem cell differentiation, epithelial cell phenotypes and fibroblast proliferation. In our study, we found that miR-497-5p was significantly upregulated both during myofibroblast differentiation of lung resident mesenchymal stem cells (LR-MSCs) and in the lung tissues of a pulmonary fibrosis model. In addition, as determined by luciferase assays and Western blot analysis, reversion-inducing cysteine-rich protein with kazal motifs (Reck) was identified to be one of the target genes of miR-497-5p, and Reck could suppress the expression of matrix metalloproteinase-2 (Mmp2) and Mmp9, which could activate latent transforming growth factor-β1 (TGF-β1)...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28062213/anti-fibrotic-effects-of-bone-morphogenetic-protein-7-modified-bone-marrow-mesenchymal-stem-cells-on-silica-induced-pulmonary-fibrosis
#5
Xiaoli Li, Guoliang An, Yan Wang, Di Liang, Zhonghui Zhu, Ximeng Lian, Piye Niu, Caixia Guo, Lin Tian
Silicosis is an occupational lung disease caused by exposure to small particles of crystalline silica, which ultimately results in diffuse pulmonary fibrosis. Evidence indicates an anti-fibrotic role of bone morphogenetic protein-7 (BMP-7) and bone marrow mesenchymal stem cells (BMSCs) in lung diseases. Therefore, strategies incorporating genetic engineering and stem cell biology might have a tremendous potential to treat critical injuries and diseases. Therefore, we modified BMSCs to overexpress the BMP-7 gene (BMP-7-BMSCs) by lentivirus transduction, and then evaluated whether fibrotic processes were inhibited by these cells in vivo...
January 4, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28056498/bone-marrow-stem-cell-therapy-partially-ameliorates-pathological-consequences-in-livers-of-mice-expressing-mutant-human-%C3%AE-1-antitrypsin
#6
Prakash Baligar, Veena Kochat, Shailendra K Arindkar, Zaffar Equbal, Snehashish Mukherjee, Swati Patel, Perumal Nagarajan, Sujata Mohanty, Jeffrey H Teckman, Asok Mukhopadhyay
: Alpha1-antitrypsin deficiency (AATD) is a genetic disease, caused by mutation of the AAT gene. Accumulation of mutated AAT protein aggregates in hepatocytes leads to endoplasmic reticulum (ER) stress resulting in impairment of liver functions and in some cases hepatocellular carcinoma, whereas decline of AAT levels in sera is responsible for pulmonary emphysema. In critical cases of liver ailments, the only option for treatment is liver transplantation, whereas AAT replacement therapy is followed in case of emphysema...
January 5, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28018357/the-role-of-lymphocytes-in-radiotherapy-induced-adverse-late-effects-in-the-lung
#7
REVIEW
Florian Wirsdörfer, Verena Jendrossek
Radiation-induced pneumonitis and fibrosis are dose-limiting side effects of thoracic irradiation. Thoracic irradiation triggers acute and chronic environmental lung changes that are shaped by the damage response of resident cells, by the resulting reaction of the immune system, and by repair processes. Although considerable progress has been made during the last decade in defining involved effector cells and soluble mediators, the network of pathophysiological events and the cellular cross talk linking acute tissue damage to chronic inflammation and fibrosis still require further definition...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28005428/telomerase-and-the-genetics-of-emphysema-susceptibility-implications-for-pathogenesis-paradigms-and-patient-care
#8
Susan E Stanley, Samantha J Merck, Mary Armanios
In the past five decades, alpha-1 antitrypsin deficiency has been the only known genetic cause of emphysema, yet it explains the genetics in only 1-2% of severe cases. Recently, mutations in telomerase genes were found to induce susceptibility to young-onset, severe, and familial emphysema at a frequency comparable to that of alpha-1 antitrypsin deficiency. Telomerase mutation carriers with emphysema report a family history of idiopathic pulmonary fibrosis, and both lung phenotypes show autosomal dominant inheritance within families...
December 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28005418/wnt-signaling-in-lung-aging-and-disease
#9
Mareike Lehmann, Hoeke A Baarsma, Melanie Königshoff
Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), represent a significant and increasing health burden. Current therapies are largely symptomatic, and novel therapeutic approaches are needed. Aging has emerged as a contributing factor for the development of both IPF and COPD because their prevalence increases with age, and several pathological features of these diseases resemble classical hallmarks of aging. Aging is thought to be driven in part by aberrant activity of developmental signaling pathways that thus might drive pathological changes, a process termed antagonistic pleiotropy or developmental drift...
December 2016: Annals of the American Thoracic Society
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
#10
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/27890713/allogeneic-human-mesenchymal-stem-cells-in-patients-with-idiopathic-pulmonary-fibrosis-via-intravenous-delivery-aether-a-phase-i-safety-clinical-trial
#11
Marilyn K Glassberg, Julia Minkiewicz, Rebecca L Toonkel, Emmanuelle S Simonet, Gustavo A Rubio, Darcy Difede, Shirin Shafazand, Aisha Khan, Marietsy V Pujol, Vincent F LaRussa, Lisa H Lancaster, Glenn D Rosen, Joel Fishman, Yolanda N Mageto, Adam Mendizabal, Joshua M Hare
BACKGROUND: Despite recent FDA approval of two new drugs for idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and mortality remains high. Pre-clinical and clinical data support the safety of human mesenchymal stem cells as a potential novel therapy for this fatal condition. The AETHER trial was the first study designed to evaluate the safety of a single infusion of bone marrow-derived mesenchymal stem cells in patients with idiopathic pulmonary fibrosis. METHODS: Nine patients with mild to moderate IPF were sequentially assigned to one of three cohorts and dosed with a single intravenous infusion of 20, 100, or 200 x 10(6) human bone marrow-derived mesenchymal stem cells per infusion from young, unrelated, male donors...
November 24, 2016: Chest
https://www.readbyqxmd.com/read/27871152/human-adipose-derived-mesenchymal-stem-cells-attenuate-early-stage-of-bleomycin-induced-pulmonary-fibrosis-comparison-with-pirfenidone
#12
Manoj Reddy, Lyle Fonseca, Shashank Gowda, Basavraj Chougule, Aarya Hari, Satish Totey
Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, invariably fatal fibrotic lung disease with no lasting option for therapy. Mesenchymal stem cells (MSCs) could be a promising modality for the treatment of IPF. Aim of the study was to investigate improvement in survivability and anti-fibrotic efficacy of human adipose-derived mesenchymal stem cells (AD-MSCs) in comparison with pirfenidone in the bleomycin-induced pulmonary fibrosis model. Methods: Human AD-MSCs were administered intravenously on day 3, 6 and 9 after an intra-tracheal challenge with bleomycin, whereas, pirfenidone was given orally in drinking water at the rate of 100 mg/kg body weight three times a day daily from day 3 onward...
November 30, 2016: International Journal of Stem Cells
https://www.readbyqxmd.com/read/27870387/primary-myelofibrosis-2017-update-on-diagnosis-risk-stratification-and-management
#13
Ayalew Tefferi
: Disease overview: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR or MPL mutation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression and shortened survival. DIAGNOSIS: Diagnosis is based on bone marrow morphology...
December 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27825158/regeneration-of-the-aging-lung-a-mini-review
#14
Sonia Navarro, Barbara Driscoll
Natural lung aging is marked by molecular changes that occur during development, maturation, and late-life decline. At the cellular and whole organ level, degenerative changes that are a hallmark of natural aging (shorter telomeres, increased expression of cellular senescence markers, increased DNA damage, oxidative stress, and apoptosis, accompanied by diminished elasticity) reach pathological levels in aging humans in the form of chronic respiratory disease. Aging strongly correlates with the development and incidence of chronic respiratory diseases, including cancer and idiopathic pulmonary fibrosis, but is most strongly linked with development of chronic obstructive pulmonary disease...
November 9, 2016: Gerontology
https://www.readbyqxmd.com/read/27824820/innate-immune-signaling-and-stem-cell-renewal-in-idiopathic-pulmonary-fibrosis
#15
Paul F Mercer, Rachel C Chambers
No abstract text is available yet for this article.
November 8, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27798371/oncostatin-m-preconditioned-mesenchymal-stem-cells-alleviate-bleomycin-induced-pulmonary-fibrosis-through-paracrine-effects-of-the-hepatocyte-growth-factor
#16
Ying-Wei Lan, Si-Min Theng, Tsung-Teng Huang, Kong-Bung Choo, Chuan-Mu Chen, Han-Pin Kuo, Kowit-Yu Chong
: : Mesenchymal stem cells (MSCs) are widely considered for treatment of pulmonary fibrosis based on the anti-inflammatory, antifibrotic, antiapoptotic, and regenerative properties of the cells. Recently, elevated levels of oncostatin M (OSM) have been reported in the bronchoalveolar lavage fluid of a pulmonary fibrosis animal model and in patients. In this work, we aimed to prolong engrafted MSC survival and to enhance the effectiveness of pulmonary fibrosis transplantation therapy by using OSM-preconditioned MSCs...
October 18, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27792269/impaired-immunosuppressive-effect-of-bronchoalveolar-mesenchymal-stem-cells-in-hypersensitivity-pneumonitis-preliminary-findings
#17
Enikő Balogh, Béla Nagy, Ágnes Gyetvai, Zsolt Bene, Zoltán Hendrik, Viktória Jeney, Péter Nagy, Ágnes Papp, József Balla, György Balla, János Kappelmayer, Béla Nagy
BACKGROUND: Bronchoalveolar mesenchymal stem cells (MSCs) play an important role in the maintenance of lung integrity. Therapeutic application of bone marrow-derived MSCs reduced chronic bronchial inflammation in idiopathic pulmonary fibrosis, and improved the ratio of survivors in sepsis with pneumonia. This study investigated the effect of MSCs from bronchoalveolar lavage fluid (BALF) of hypersensitivity pneumonitis (HP) on T-cell function under in vitro conditions. METHODS: Bronchoalveolar MSCs were obtained via bronchoscopy with BAL from children with severe subacute HP...
October 28, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27780343/gene-editing-and-genetic-lung-disease-basic-research-meets-therapeutic-application
#18
Deepthi Alapati, Edward E Morrisey
While our understanding of the genetics and pathology of congenital lung diseases such as surfactant protein deficiency, cystic fibrosis and alpha 1 antitrypsin deficiency is extensive, treatment options are lacking. Since the lung is a barrier organ in direct communication with the external environment, targeted delivery of gene corrective technologies to the respiratory system via intra-tracheal or intranasal routes is an attractive option for therapy. CRISPR/Cas9 gene editing technology is a promising approach to repair or inactivate disease causing mutations...
October 25, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27754275/sy-18-1-translational-research-in-pah
#19
Wook-Jin Chung
Pulmonary arterial hypertension (PAH) is a life-threatening disorder with a poor prognosis and causes pulmonary vascular remodeling accompanied with increased pulmonary arterial medial wall thickness and fibrosis, which leads to vascular and right ventricular (RV) dysfunction. Despite treatment with prostacyclin, endothelin antagonist, and phosphodiesterase-5 inhibitors the 1-year mortality rate of PAH still remains high. Recent registries, clinical trials, and basic researches have been increasing the knowledge of PAH and it would contribute to potential therapeutic strategies and better clinical outcome...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27694932/hyaluronan-and-tlr4-promote-surfactant-protein-c-positive-alveolar-progenitor-cell-renewal-and-prevent-severe-pulmonary-fibrosis-in-mice
#20
Jiurong Liang, Yanli Zhang, Ting Xie, Ningshan Liu, Huaiyong Chen, Yan Geng, Adrianne Kurkciyan, Jessica Monterrosa Mena, Barry R Stripp, Dianhua Jiang, Paul W Noble
Successful recovery from lung injury requires the repair and regeneration of alveolar epithelial cells to restore the integrity of gas-exchanging regions within the lung and preserve organ function. Improper regeneration of the alveolar epithelium is often associated with severe pulmonary fibrosis, the latter of which involves the recruitment and activation of fibroblasts, as well as matrix accumulation. Type 2 alveolar epithelial cells (AEC2s) are stem cells in the adult lung that contribute to the lung repair process...
November 2016: Nature Medicine
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