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Stem cell pulmonary fibrosis

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https://www.readbyqxmd.com/read/29463756/diagnostic-utility-of-telomere-length-testing-in-a-hospital-based-setting
#1
Jonathan K Alder, Vidya Sagar Hanumanthu, Margaret A Strong, Amy E DeZern, Susan E Stanley, Clifford M Takemoto, Ludmilla Danilova, Carolyn D Applegate, Stephen G Bolton, David W Mohr, Robert A Brodsky, James F Casella, Carol W Greider, J Brooks Jackson, Mary Armanios
Telomere length (TL) predicts the onset of cellular senescence in vitro but the diagnostic utility of TL measurement in clinical settings is not fully known. We tested the value of TL measurement by flow cytometry and FISH (flowFISH) in patients with mutations in telomerase and telomere maintenance genes. TL had a discrete and reproducible normal range with definable upper and lower boundaries. While TL above the 50th age-adjusted percentile had a 100% negative predictive value for clinically relevant mutations, the lower threshold in mutation carriers was age-dependent, and adult mutation carriers often overlapped with the lowest decile of controls...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29412521/longitudinal-outcomes-of-patients-enrolled-in-a-phase-ib-clinical-trial-of-the-adipose-derived-stromal-cells-stromal-vascular-fraction-in-idiopathic-pulmonary-fibrosis
#2
Paschalis Ntolios, Eleni Manoloudi, Argyris Tzouvelekis, Evangelos Bouros, Pachalis Steiropoulos, Stavros Anevlavis, Demosthenes Bouros, Marios E Froudarakis
BACKGROUND: Cell based therapies have been used for the management of several diseases, holding promising results. Few studies have evaluated their use in chronic lung diseases. Idiopathic Pulmonary Fibrosis (IPF) remains a lethal disease, although new therapies have emerged the recent years. We have recently published a phase I study of 14 patients receiving endobronchially Adipose-Derived Stem Cells (ADSCs). The aim of the current report is to assess the outcome for our patient population...
February 7, 2018: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/29297621/amnion-epithelial-cell-derived-exosomes-restrict-lung-injury-and-enhance-endogenous-lung-repair
#3
Jean L Tan, Sin N Lau, Bryan Leaw, Hong P T Nguyen, Lois A Salamonsen, Mohamed I Saad, Siow T Chan, Dandan Zhu, Mirja Krause, Carla Kim, William Sievert, Euan M Wallace, Rebecca Lim
Idiopathic pulmonary fibrosis (IPF) is characterized by chronic inflammation, severe scarring, and stem cell senescence. Stem cell-based therapies modulate inflammatory and fibrogenic pathways by release of soluble factors. Stem cell-derived extracellular vesicles should be explored as a potential therapy for IPF. Human amnion epithelial cell-derived exosomes (hAEC Exo) were isolated and compared against human lung fibroblasts exosomes. hAEC Exo were assessed as a potential therapy for lung fibrosis. Exosomes were isolated and evaluated for their protein and miRNA cargo...
January 3, 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29296972/bone-marrow-transplantation-prevents-right-ventricle-disease-in-the-caveolin-1-deficient-mouse-model-of-pulmonary-hypertension
#4
Kewal Asosingh, Nicholas Wanner, Kelly Weiss, Kimberly Queisser, Liya Gebreab, Biruk Kassa, Eric Stuehr, Brian Graham, Serpil Erzurum
Accumulating evidence shows a causative role for the bone marrow (BM) in the genesis and progression of pulmonary hypertension (PH). Engraftment of BM hematopoietic stem cells from PH patients to mice reproduces the cardiopulmonary pathology of PH. However, it is unknown whether healthy BM can prevent the development of right heart disease. Caveolin-1-deficient (CAV-1 KO) mice develop cardiopulmonary disease with manifestations resembling PH, including elevated right ventricular (RV) systolic pressure (RVSP), RV hypertrophy, and pulmonary endothelial proliferative disease...
March 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29291140/mesenchymal-stem-cell-soluble-mediators-and-cystic-fibrosis
#5
Morgan T Sutton, David Fletcher, Nicole Episalla, Lauren Auster, Sukhmani Kaur, Mary Chandler Gwin, Michael Folz, Dante Velasquez, Varun Roy, Rolf van Heeckeren, Donald P Lennon, Arnold I Caplan, Tracey L Bonfield
Human Mesenchymal stem cells (hMSCs) secrete products (supernatants) that are anti-inflammatory and antimicrobial. We have previously shown that hMSCs decrease inflammation and Pseudomonas aeruginosa infection in the in vivo murine model of Cystic Fibrosis (CF). Cystic Fibrosis (CF) is a genetic disease in which pulmonary infection and inflammation becomes the major cause of morbidity and mortality. Our studies focus on determining how MSCs contribute to improved outcomes in the CF mouse model centering on how the MSCs impact the inflammatory response to pathogenic organisms...
August 2017: Journal of Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29273797/thy-1-dependent-uptake-of-mesenchymal-stem-cell-derived-extracellular-vesicles-blocks-myofibroblastic-differentiation
#6
Tzu-Pin Shentu, Tse-Shun Huang, Mateja Cernelc-Kohan, Joy Chan, Simon S Wong, Celia R Espinoza, Chunting Tan, Irene Gramaglia, Henri van der Heyde, Shu Chien, James S Hagood
Bone marrow-derived mesenchymal stem cells (MSC) have been promoted for multiple therapeutic applications. Many beneficial effects of MSCs are paracrine, dependent on extracellular vesicles (EVs). Although MSC-derived EVs (mEVs) are beneficial for acute lung injury and pulmonary fibrosis, mechanisms of mEV uptake by lung fibroblasts and their effects on myofibroblastic differentiation have not been established. We demonstrate that mEVs, but not fibroblast EVs (fEVs), suppress TGFβ1-induced myofibroblastic differentiation of normal and idiopathic pulmonary fibrosis (IPF) lung fibroblasts...
December 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29236513/depletion-of-airway-submucosal-glands-and-tp63-krt5-basal-cells-in-obliterative-bronchiolitis
#7
Anthony M Swatek, Thomas J Lynch, Adrianne K Crooke, Preston J Anderson, Scott R Tyler, Leonard Brooks, Marina Ivanovic, Julia A Klesney-Tait, Michael Eberlein, Tahuanty Pena, David K Meyerholz, John F Engelhardt, Kalpaj R Parekh
RATIONALE: Obliterative bronchiolitis (OB) is a major cause of mortality following lung transplantation. Depletion of airway stem cells (SCs) may lead to fibrosis in OB. OBJECTIVE: Two major SC compartments in airways are submucosal glands (SMGs) and surface airway TP63+(p63)/KRT5+(K5) basal cells (BCs). We hypothesized that depletion of these SC compartments occurs in OB. METHODS: Ferret orthotopic left lung transplants were used as an experimental model of OB, and findings were corroborated in human lung allografts...
December 13, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29220578/pd-1-pd-l1-pathway-mediates-the-alleviation-of-pulmonary-fibrosis-by-human-mesenchymal-stem-cells-in-humanized-mice
#8
Ke Ni, Ming Liu, Jian Zheng, Liyan Wen, Qingyun Chen, Zheng Xiang, Kowk-Tai Lam, Yinping Liu, Godfrey Chi-Fung Chan, Yu-Lung Lau, Wenwei Tu
RATIONALE: Pulmonary fibrosis is a chronic progressive lung disease with few treatments. Human mesenchymal stem cells (MSC) have been shown to be beneficial to pulmonary fibrosis as they have the immunomodulatory capacity. However, there is no reliable model to test the therapeutic effect of human MSC in vivo. METHODS: Here, to mimic pulmonary fibrosis in humans, we established a novel bleomycin-induced pulmonary fibrosis model in humanized mice. Based on this model, the benefit of human MSC to pulmonary fibrosis and underlying mechanism were investigated...
December 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29207055/therapeutic-effects-of-conditioned-medium-from-bone-marrow-derived-mesenchymal-stem-cells-on-epithelial-mesenchymal-transition-in-a549-cells
#9
Xin Wang, Jun-Ling Gao, Man-Man Zhao, Hui-Xing Zhu, Yan-Xia Tian, Ran Li, Xiao-Hua Jiang, Lei Yu, Jing-Rui Tian, Jian-Zhong Cui
Pulmonary fibrosis (PF) is a chronic lung disease. The transforming growth factor-β1 (TGF-β1)/Smad3 signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis. Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to be a modulator of the molecular aspects of the fibrosis pathway. However, it is still unknown as to whether the conditioned medium from BMSCs (BMSCs-CM) inhibits the epithelial-mesenchymal transition (EMT) process. This study confirmed the hypothesis that BMSCs-CM exerts an anti-fibrotic effect on human type II alveolar epithelial cells (A549) by suppressing the phosphorylation of Smad3...
November 24, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29183009/hypoxia-induced-mesenchymal-stromal-cells-exhibit-an-enhanced-therapeutic-effect-on-radiation-induced-lung-injury-in-mice-due-to-an-increased-proliferation-potential-and-enhanced-antioxidant-ability
#10
Bailong Li, Cheng Li, Mo Zhu, Youjun Zhang, Jicong Du, Yang Xu, Bin Liu, Fu Gao, Hu Liu, Jianming Cai, Yanyong Yang
BACKGROUND/AIMS: Radiation therapy is an important treatment for thoracic cancer; however, side effects accompanied with radiotherapy lead to limited tumor control and a decline in patient quality of life. Among these side effects, radiation-induced lung injury (RILI) is the most serious and common. Hence, an effective remedy for RILI is needed. Mesenchymal stromal cells (MSCs) are multipotent adult stem cells that have been demonstrated to be an effective treatment in some disease caused by tissue damage...
November 29, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29167193/airway-transplantation-of-adipose-stem-cells-protects-against-bleomycin-induced-pulmonary-fibrosis
#11
Pedro Llontop, Daniel Lopez-Fernandez, Bernardino Clavo, Juan Luis Afonso Martín, María D Fiuza-Pérez, Mariano García Arranz, Joaquín Calatayud, Laureano Molins López-Rodó, Khalid Alshehri, Adil Ayub, Wissam Raad, Faiz Bhora, Norberto Santana-Rodríguez
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis. Adipose-derived stem cells (ADSC) have demonstrated regenerative properties in several tissues. The hypothesis of this study was that airway transplantation of ADSC could protect against bleomycin (BLM)-induced pulmonary fibrosis (PF). Fifty-eight lungs from 29 male Sprague-Dawley rats were analyzed. Animals were randomly divided into five groups: a) control (n=3); b) sham (n=6); c) BLM (n=6); d) BLM+ADSC-2d (n=6); and e) BLM+ADSC-14d (n=8)...
November 21, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/29167125/mesenchymal-stem-cells-reduce-hypoxia-induced-apoptosis-in-alveolar-epithelial-cells-by-modulating-hif-and-ros-hypoxic-signalings
#12
Olivier Bernard, Florence Jeny, Yurdagul Uzunhan, Elisabetta Dondi, Rahma Terfous, Rabab Label, Angela Sutton, Jérôme Larghero, Valérie Vanneaux, Hilario Nunes, Emilie Boncoeur, Carole Planès, Nicolas Dard
Distal lung diseases such as pulmonary fibrosis or acute lung injury are commonly associated with local alveolar hypoxia that may be deleterious through the stimulation of alveolar epithelial cell (AEC) apoptosis. In various murine models of alveolar injury, administration of allogenic human mesenchymal stem cells (hMSC) exerts an overall protective paracrine effect limiting lung inflammation and fibrosis. However, the precise mechanisms on lung cells themselves remain poorly understood. Here we investigated whether hMSC conditioned medium (hMSC-CM) would protect AECs from hypoxia-induced apoptosis and the mechanisms involved in this cytoprotective effect...
November 22, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
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
#13
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...
October 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29097816/anti-inflammatory-and-anti-fibrotic-effects-of-intravenous-adipose-derived-stem-cell-transplantation-in-a-mouse-model-of-bleomycin-induced-interstitial-pneumonia
#14
Takuya Kotani, Ryota Masutani, Takayasu Suzuka, Katsuhiro Oda, Shigeki Makino, Masaaki Ii
Adipose-derived stem cells (AdSCs) have recently been considered a useful treatment tool for autoimmune disease because of their anti-inflammatory and immunosuppressive effects. We investigated the therapeutic effect of intravenous AdSC transplantation in a mouse model of bleomycin-induced lung injury. AdSCs accumulated in the pulmonary interstitium and inhibited both inflammation and fibrosis in the lung, markedly improving the survival rate of mice with bleomycin-induced lung injury in a cell number-dependent manner...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29045045/mesenchymal-stromal-cell-therapy-in-bronchopulmonary-dysplasia-systematic-review-and-meta-analysis-of-preclinical-studies
#15
Sajit Augustine, Marc T Avey, Brittany Harrison, Tiffany Locke, Mona Ghannad, David Moher, Bernard Thébaud
Extreme prematurity is the leading cause of death among children under 5 years of age. Currently, there is no treatment for bronchopulmonary dysplasia (BPD), the most common complication of extreme prematurity. Experimental studies in animal models of BPD suggest that mesenchymal stromal cells (MSCs) are lung protective. To date, no systematic review and meta-analysis has evaluated the preclinical evidence of this promising therapy. Our protocol was registered with Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies prior to searching MEDLINE (1946 to June 1, 2015), Embase (1947 to 2015 Week 22), Pubmed, Web of Science, and conference proceedings (1990 to present) for controlled comparative studies of neonatal animal models that received MSCs or cell free MSC-derived conditioned media (MSC-CM)...
October 17, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29044226/bone-marrow-transplant-induced-alterations-in-notch-signaling-promote-pathologic-th17-responses-to-%C3%AE-herpesvirus-infection
#16
S J Gurczynski, X Zhou, M Flaherty, C A Wilke, B B Moore
Idiopathic pneumonia syndrome (IPS) is a common, often fatal, complication following hematopoietic stem cell transplantation (HSCT) characterized by severe pneumonitis and interstitial fibrosis. Fully reconstituted syngeneic bone marrow transplant (BMT) mice infected with murine γ-herpesvirus-68 develop interleukin-17 (IL-17)-driven pneumonitis and fibrosis, which mimics clinical manifestations of IPS. We found CD103+ and CD11b+ dendritic cells (DCs) are selectively deficient for the Notch ligand, DLL4, following BMT and CD4+ T cells isolated from lungs and spleens of infected BMT mice display Notch signaling defects...
October 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29040281/impaired-anti-fibrotic-effect-of-bone-marrow-derived-mesenchymal-stem-cell-in-a-mouse-model-of-pulmonary-paracoccidioidomycosis
#17
Julián Camilo Arango, Juan David Puerta-Arias, Paula Andrea Pino-Tamayo, Lina María Salazar-Peláez, Mauricio Rojas, Ángel González
Bone marrow-derived mesenchymal stem cells (BMMSCs) have been consider as a promising therapy in fibrotic diseases. Experimental models suggest that BMMSCs may be used as an alternative therapy to treat chemical- or physical-induced pulmonary fibrosis. We investigated the anti-fibrotic potential of BMMSCs in an experimental model of lung fibrosis by infection with Paracoccidioides brasiliensis. BMMSCs were isolated and purified from BALB/c mice using standardized methods. BALB/c male mice were inoculated by intranasal infection of 1...
October 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28991645/lung-diseases-of-the-elderly-cellular-mechanisms
#18
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
#19
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...
November 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
#20
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
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