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Stem cell pulmonary fibrosis

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https://www.readbyqxmd.com/read/28991645/lung-diseases-of-the-elderly-cellular-mechanisms
#1
REVIEW
Kori Ascher, Sharon J Elliot, Gustavo A Rubio, Marilyn K Glassberg
Natural lung aging is characterized by molecular and cellular changes in multiple lung cell populations. These changes include shorter telomeres, increased expression of cellular senescence markers, increased DNA damage, oxidative stress, apoptosis, and stem cell exhaustion. Aging, combined with the loss of protective repair processes, correlates with the development and incidence of chronic respiratory diseases, including idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease. Ultimately, it is the interplay of age-related changes in biology and the subsequent responses to environmental exposures that largely define the physiology and clinical course of the aging lung...
November 2017: Clinics in Geriatric Medicine
https://www.readbyqxmd.com/read/28983101/emerging-therapies-for-idiopathic-pulmonary-fibrosis-a-progressive-age-related-disease
#2
REVIEW
Ana L Mora, Mauricio Rojas, Annie Pardo, Moises Selman
Idiopathic pulmonary fibrosis (IPF) is a fatal age-associated disease that is characterized by progressive and irreversible scarring of the lung. The pathogenesis of IPF is not completely understood and current therapies are limited to those that reduce the rate of functional decline in patients with mild-to-moderate disease. In this context, new therapeutic approaches that substantially improve the survival time and quality of life of these patients are urgently needed. Our incomplete understanding of the pathogenic mechanisms of IPF and the lack of appropriate experimental models that reproduce the key characteristics of the human disease are major challenges...
October 6, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28969530/successful-second-unrelated-donor-hematopoietic-stem-cell-transplant-in-a-patient-with-dyskeratosis-congenital-after-first-graft-rejection
#3
Stefano Giardino, Maura Faraci, Edoardo Lanino, Giuseppe Morreale, Paola Terranova, Elena Palmisani, Carlo Dufour, Maurizio Miano
Dyskeratosis congenita is a rare congenital telomeropathy characterized by cutaneous and nail dystrophy, oral leukoplakia, and bone marrow failure. Pulmonary fibrosis and cancers are late manifestations. Allogeneic hematopoietic stem cell transplant represents the only cure for those with bone marrow failure with this disease, but outcomes reported are overall poor, with organ toxicities, graft failure, and graft-versus-host disease as main issues. Although reduced intensity conditioning regimens seem to be related to better outcomes, a standard regimen for dyskeratosis congenita has never been defined...
September 30, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28951564/mechanobiology-of-yap-and-taz-in-physiology-and-disease
#4
REVIEW
Tito Panciera, Luca Azzolin, Michelangelo Cordenonsi, Stefano Piccolo
A growing body of evidence suggests that mechanical signals emanating from the cell's microenvironment are fundamental regulators of cell behaviour. Moreover, at the macroscopic scale, the influence of forces, such as the forces generated by blood flow, muscle contraction, gravity and overall tissue rigidity (for example, inside of a tumour lump), is central to our understanding of physiology and disease pathogenesis. Still, how mechanical cues are sensed and transduced at the molecular level to regulate gene expression has long remained enigmatic...
September 27, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28882120/clinical-and-radiological-characteristics-of-patients-with-late-onset-severe-restrictive-lung-defect-after-hematopoietic-stem-cell-transplantation
#5
Ho Namkoong, Makoto Ishii, Takehiko Mori, Hiroaki Sugiura, Sadatomo Tasaka, Masatoshi Sakurai, Yuya Koda, Jun Kato, Naoki Hasegawa, Shinichiro Okamoto, Tomoko Betsuyaku
BACKGROUND: Late-onset noninfectious pulmonary complications (LONIPCs), which occur more than 3 months after allogeneic hematopoietic stem cell transplantation (HSCT), are major causes of morbidity and mortality after transplantation. Among LONIPCs, we occasionally treat patients with late-onset severe restrictive lung defect after HSCT; however, its clinical features have not been fully elucidated. METHODS: A retrospective chart review of a single center on cases of late-onset severe restrictive lung defect after HSCT was performed...
September 7, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28870520/loss-of-nrf2-promotes-alveolar-type-2-cell-loss-in-irradiated-fibrotic-lung
#6
Geri Traver, Stacey Mont, David Gius, William E Lawson, George X Ding, Konjeti R Sekhar, Michael L Freeman
The development of radiation-induced pulmonary fibrosis represents a critical clinical issue limiting delivery of therapeutic doses of radiation to non-small cell lung cancer. Identification of the cell types whose injury initiates a fibrotic response and the underlying biological factors that govern that response are needed for developing strategies that prevent or mitigate fibrosis. C57BL/6 mice (wild type, Nrf2 null, Nrf2(flox/flox), and Nrf2(Δ/Δ); SPC-Cre) were administered a thoracic dose of 12Gy and allowed to recover for 250 days...
November 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28853608/mesenchymal-stromal-cell-exosomes-ameliorate-experimental-bronchopulmonary-dysplasia-and-restore-lung-function-through-macrophage-immunomodulation
#7
Gareth R Willis, Angeles Fernandez-Gonzalez, Jamie Anastas, Sally H Vitali, Xianlan Liu, Maria Ericsson, April Kwong, S Alex Mitsialis, Stella Kourembanas
RATIONALE: Mesenchymal stem/stromal cell (MSC) therapies have shown promise in preclinical models of pathologies relevant to newborn medicine, such as bronchopulmonary dysplasia (BPD). We have reported that the therapeutic capacity of MSCs is comprised in their secretome, and demonstrated that the therapeutic vectors are exosomes produced by MSCs (MSC-exos). OBJECTIVE: To assess efficacy of MSC-exo treatment in a pre-clinical model of BPD and to investigate mechanisms underlying MSC-exo therapeutic action...
August 30, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28831189/a-comparative-analysis-of-longitudinal-computed-tomography-and-histopathology-for-evaluating-the-potential-of-mesenchymal-stem-cells-in-mitigating-radiation-induced-pulmonary-fibrosis
#8
Jessica R Perez, Sangkyu Lee, Norma Ybarra, Ola Maria, Monica Serban, Krishinima Jeyaseelan, Li Ming Wang, Jan Seuntjens, Issam El Naqa
Radiation-induced pulmonary fibrosis (RIPF) is a debilitating side effect that occurs in up to 30% of thoracic irradiations in breast and lung cancer patients. RIPF remains a major limiting factor to dose escalation and an obstacle to applying more promising new treatments for cancer cure. Limited treatment options are available to mitigate RIPF once it occurs, but recently, mesenchymal stem cells (MSCs) and a drug treatment stimulating endogenous stem cells (GM-CSF) have been investigated for their potential in preventing this disease onset...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28783251/safety-and-efficacy-of-allogeneic-lung-spheroid-cells-in-a-mismatched-rat-model-of-pulmonary-fibrosis
#9
Jhon Cores, M Taylor Hensley, Kathryn Kinlaw, S Michaela Rikard, Phuong-Uyen Dinh, Dipti Paudel, Junnan Tang, Adam C Vandergriff, Tyler A Allen, Yazhou Li, Jianhua Liu, Bo Niu, Yuepeng Chi, Thomas Caranasos, Leonard J Lobo, Ke Cheng
Idiopathic pulmonary fibrosis is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix causing lung distortions and dysfunctions. The prognosis after detection is merely 3-5 years and the only two Food and Drug Administration-approved drugs treat the symptoms, not the disease, and have numerous side effects. Stem cell therapy is a promising treatment strategy for pulmonary fibrosis. Current animal and clinical studies focus on the use of adipose or bone marrow-derived mesenchymal stem cells...
August 7, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28731277/tnf-%C3%AE-induced-nf-%C3%AE%C2%BAb-activation-promotes-myofibroblast-differentiation-of-lr-mscs-and-exacerbates-bleomycin-induced-pulmonary-fibrosis
#10
Jiwei Hou, Tan Ma, Honghui Cao, Yabing Chen, Cong Wang, Xiang Chen, Zou Xiang, Xiaodong Han
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible lung disease of unknown cause. It has been reported that both lung resident mesenchymal stem cells (LR-MSCs) and tumor necrosis factor-α (TNF-α) play important roles in the development of pulmonary fibrosis. However, the underlying connections between LR-MSCs and TNF-α in the pathogenesis of pulmonary fibrosis are still elusive. In this study, we found that the pro-inflammatory cytokine TNF-α and the transcription factor nuclear factor kappa B (NF-κB) p65 subunit were both upregulated in bleomycin-induced fibrotic lung tissue...
July 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28700752/role-of-a-novel-immune-modulating-ddr2-expressing-population-in-silica-induced-pulmonary-fibrosis
#11
Lindsay T McDonald, Sara D Johnson, Dayvia L Russell, M Rita I Young, Amanda C LaRue
Micro-injuries associated with chronic inhaled particle exposures are linked with activation of the immune response and are thought to contribute to progression of fibrotic disease. In the pulmonary environment, we have previously demonstrated a heterogeneous population of circulating fibroblast precursors (CFPs), which are defined by expression of the pan-leukocyte marker CD45 and the collagen receptor, discoidin domain receptor-2 (DDR2). This population is derived from the hematopoietic stem cell, expresses collagen, and has a fibroblastic morphology in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28675062/lung-regeneration-using-amniotic-fluid-mesenchymal-stem-cells
#12
Alireza Azargoon, Babak Negahdari
Respiratory diseases, such as chronic obstructive pulmonary disease (COPD), pulmonary hypertension and lung fibrosis, are yet a major challenge in the world and they result in irreversible structural lung damage. Lung transplantation as the only therapeutic option face some major challenges like graft rejection and cancer, arising as a result of immunosuppression. A low survival rate faced by lung transplantation patients is presently limited to approximately 5 years. Lungs shortage therefore calls for a mechanism that would increase the availability of suitable organs for transplantation...
July 4, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28666430/derivation-of-therapeutic-lung-spheroid-cells-from-minimally-invasive-transbronchial-pulmonary-biopsies
#13
Phuong-Uyen C Dinh, Jhon Cores, M Taylor Hensley, Adam C Vandergriff, Junnan Tang, Tyler A Allen, Thomas G Caranasos, Kenneth B Adler, Leonard J Lobo, Ke Cheng
BACKGROUND: Resident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popular cell therapy product for the treatment of lung diseases. Surgical lung biopsies can be the tissue source but such procedures carry a high risk of mortality. METHODS: In this study we demonstrate that therapeutic lung cells, termed "lung spheroid cells" (LSCs) can be generated from minimally invasive transbronchial lung biopsies using a three-dimensional culture technique...
June 30, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28662409/human-placental-mesenchymal-stem-cells-of-fetal-origins-alleviated-inflammation-and-fibrosis-by-attenuating-myd88-signaling-in-bleomycin-induced-pulmonary-fibrosis-mice
#14
Feng Li, Fei Han, Hui Li, Jia Zhang, Xia Qiao, Juan Shi, Li Yang, Jianda Dong, Meihui Luo, Jun Wei, Xiaoming Liu
Pulmonary fibrosis is a progressive lung disease that its pathogenic mechanism currently is incompletely understood. Toll-like receptor (TLR) signaling has recently been identified as a regulator of inflammation and pulmonary fibrosis. In addition, mesenchymal stem cells (MSCs) of different origins offer a great promise in treatment of idiopathic pulmonary fibrosis (IPF). However mechanisms of pathogenic roles of TLR signaling and therapeutic effects of MSCs in the IPF remain elusive. In present study, the involvement of TLR signaling and the therapeutic role of MSCs were interrogated in MyD88-deficient mice using human placental MSCs of fetal origins (hfPMSCs)...
October 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28659506/cell-therapy-for-lung-disease
#15
Sabine Geiger, Daniela Hirsch, Felix G Hermann
Besides cancer and cardiovascular diseases, lung disorders are a leading cause of morbidity and death worldwide. For many disease conditions no effective and curative treatment options are available. Cell therapies offer a novel therapeutic approach due to their inherent anti-inflammatory and anti-fibrotic properties. Mesenchymal stem/stromal cells (MSC) are the most studied cell product. Numerous preclinical studies demonstrate an improvement of disease-associated parameters after MSC administration in several lung disorders, including chronic obstructive pulmonary disease, acute respiratory distress syndrome and idiopathic pulmonary fibrosis...
June 30, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28586311/mesenchymal-stem-cells-in-idiopathic-pulmonary-fibrosis
#16
REVIEW
Xiaohong Li, Shaojie Yue, Ziqiang Luo
Idiopathic pulmonary fibrosis (IPF) is a major cause of respiratory failure in critically ill patients and common outcome of various lung interstitial diseases. Its mortality remains high, and no effective pharmacotherapy, in addition to artificial ventilation and transplantation, exists. As such, the administration of mesenchymal stem or stromal cells (MSCs) is currently investigated as a new therapeutic method for pulmonary fibrosis. Clinical trials on MSC-based therapy as a potential treatment for lung injury and fibrosis are also performed...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28565787/clinical-observation-of-umbilical-cord-mesenchymal-stem-cell-treatment-of-severe-idiopathic-pulmonary-fibrosis-a-case-report
#17
Chunyu Zhang, Xiaoguang Yin, Jinghan Zhang, Qiang Ao, Yongquan Gu, Ying Liu
Idiopathic pulmonary fibrosis (IPF) is a degenerative disease characterized by fibrosis. Cell therapy has been considered within the therapeutic options for IPF. In this study, we explored the potential benefits of human umbilical cord-derived mesenchymal stem cell (HUC-MSC) intravenous infusion in the management of IPF. We describe a case of a 56-year-old man with IPF who was receiving long-term oxygen therapy (LTOT). The patient underwent HUC-MSC intravenous infusion and was followed up for 12 months. Clinical and motor tests, as well as questionnaires assessing quality of life, were performed prior to and following the transplantation...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28529637/role-of-the-cxcl8-cxcr1-2-axis-in-cancer-and-inflammatory-diseases
#18
REVIEW
Helen Ha, Bikash Debnath, Nouri Neamati
The chemokine receptors CXCR1/2 and their ligand CXCL8 are essential for the activation and trafficking of inflammatory mediators as well as tumor progression and metastasis. The CXCL8-CXCR1/2 signaling axis is involved in the pathogenesis of several diseases including chronic obstructive pulmonary diseases (COPD), asthma, cystic fibrosis and cancer. Interaction between CXCL8 secreted by select cancer cells and CXCR1/2 in the tumor microenvironment is critical for cancer progression and metastasis. The CXCL8-CXCR1/2 axis may play an important role in tumor progression and metastasis by regulating cancer stem cell (CSC) proliferation and self-renewal...
2017: Theranostics
https://www.readbyqxmd.com/read/28507545/clinical-and-molecular-heterogeneity-of-rtel1-deficiency
#19
Carsten Speckmann, Sushree Sangita Sahoo, Marta Rizzi, Shinsuke Hirabayashi, Axel Karow, Nina Kathrin Serwas, Marc Hoemberg, Natalja Damatova, Detlev Schindler, Jean-Baptiste Vannier, Simon J Boulton, Ulrich Pannicke, Gudrun Göhring, Kathrin Thomay, J J Verdu-Amoros, Holger Hauch, Wilhelm Woessmann, Gabriele Escherich, Eckart Laack, Liliana Rindle, Maximilian Seidl, Anne Rensing-Ehl, Ekkehart Lausch, Christine Jandrasits, Brigitte Strahm, Klaus Schwarz, Stephan R Ehl, Charlotte Niemeyer, Kaan Boztug, Marcin W Wlodarski
Typical features of dyskeratosis congenita (DC) resulting from excessive telomere shortening include bone marrow failure (BMF), mucosal fragility, and pulmonary or liver fibrosis. In more severe cases, immune deficiency and recurring infections can add to disease severity. RTEL1 deficiency has recently been described as a major genetic etiology, but the molecular basis and clinical consequences of RTEL1-associated DC are incompletely characterized. We report our observations in a cohort of six patients: five with novel biallelic RTEL1 mutations p...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28487390/activation-of-the-amino-acid-response-pathway-blunts-the-effects-of-cardiac-stress
#20
Pu Qin, Pelin Arabacilar, Roberta E Bernard, Weike Bao, Alan R Olzinski, Yuanjun Guo, Hind Lal, Stephen H Eisennagel, Michael C Platchek, Wensheng Xie, Julius Del Rosario, Mohamad Nayal, Quinn Lu, Theresa Roethke, Christine G Schnackenberg, Fe Wright, Michael P Quaile, Wendy S Halsey, Ashley M Hughes, Ganesh M Sathe, George P Livi, Robert B Kirkpatrick, Xiaoyan A Qu, Deepak K Rajpal, Maria Faelth Savitski, Marcus Bantscheff, Gerard Joberty, Giovanna Bergamini, Thomas L Force, Gregory J Gatto, Erding Hu, Robert N Willette
BACKGROUND: The amino acid response (AAR) is an evolutionarily conserved protective mechanism activated by amino acid deficiency through a key kinase, general control nonderepressible 2. In addition to mobilizing amino acids, the AAR broadly affects gene and protein expression in a variety of pathways and elicits antifibrotic, autophagic, and anti-inflammatory activities. However, little is known regarding its role in cardiac stress. Our aim was to investigate the effects of halofuginone, a prolyl-tRNA synthetase inhibitor, on the AAR pathway in cardiac fibroblasts, cardiomyocytes, and in mouse models of cardiac stress and failure...
May 9, 2017: Journal of the American Heart Association
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