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https://www.readbyqxmd.com/read/29607186/stem-cell-therapies-for-chronic-obstructive-pulmonary-disease-current-status-of-pre-clinical-studies-and-clinical-trials
#1
REVIEW
Zhongwei Sun, Feng Li, Xin Zhou, Kian Fan Chung, Wen Wang, Jialun Wang
Chronic obstructive pulmonary disease (COPD) is a respiratory disease that has a major impact worldwide. The currently-available drugs mainly focus on relieving the symptoms of COPD patients. Novel regenerative therapeutic approaches have been investigated with the aim of repairing or replacing the injured functional structures of the respiratory system. We summarized the progress made by regenerative therapies for COPD by analyzing results from both pre-clinical studies and completed clinical trials. These approaches include the application of exogenous stem cells or small molecules to stimulate the regeneration by endogenous lung stem/progenitor cells...
February 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29420258/single-cell-wnt-signaling-niches-maintain-stemness-of-alveolar-type-2-cells
#2
Ahmad N Nabhan, Douglas G Brownfield, Pehr B Harbury, Mark A Krasnow, Tushar J Desai
Alveoli, the lung's respiratory units, are tiny sacs where oxygen enters the bloodstream. They are lined by flat alveolar type 1 (AT1) cells, which mediate gas exchange, and AT2 cells, which secrete surfactant. Rare AT2s also function as alveolar stem cells. We show that AT2 lung stem cells display active Wnt signaling, and many of them are near single, Wnt-expressing fibroblasts. Blocking Wnt secretion depletes these stem cells. Daughter cells leaving the Wnt niche transdifferentiate into AT1s: Maintaining Wnt signaling prevents transdifferentiation, whereas abrogating Wnt signaling promotes it...
March 9, 2018: Science
https://www.readbyqxmd.com/read/29341112/conditionally-reprogrammed-cells-crc-methodology-does-not-allow-the-in-vitro-expansion-of-patient-derived-primary-and-metastatic-lung-cancer-cells
#3
Giovanni Sette, Valentina Salvati, Ilenia Giordani, Emanuela Pilozzi, Denise Quacquarini, Enrico Duranti, Francesca De Nicola, Matteo Pallocca, Maurizio Fanciulli, Mario Falchi, Roberto Pallini, Ruggero De Maria, Adriana Eramo
Availability of tumor and non-tumor patient-derived models would promote the development of more effective therapeutics for non-small cell lung cancer (NSCLC). Recently, conditionally reprogrammed cells (CRC) methodology demonstrated exceptional potential for the expansion of epithelial cells from patient tissues. However, the possibility to expand patient-derived lung cancer cells using CRC protocols is controversial. Here, we used CRC approach to expand cells from non-tumoral and tumor biopsies of patients with primary or metastatic NSCLC as well as pulmonary metastases of colorectal or breast cancers...
January 17, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29126435/human-amnion-cells-reverse-acute-and-chronic-pulmonary-damage-in-experimental-neonatal-lung-injury
#4
Dandan Zhu, Jean Tan, Amina S Maleken, Ruth Muljadi, Siow T Chan, Sin N Lau, Kirstin Elgass, Bryan Leaw, Joanne Mockler, Daniel Chambers, Kristen T Leeman, Carla F Kim, Euan M Wallace, Rebecca Lim
BACKGROUND: Despite advances in neonatal care, bronchopulmonary dysplasia (BPD) remains a significant contributor to infant mortality and morbidity. While human amnion epithelial cells (hAECs) have shown promise in small and large animal models of BPD, there is scarce information on long-term benefit and clinically relevant questions surrounding administration strategy remain unanswered. In assessing the therapeutic potential of hAECs, we investigated the impact of cell dosage, administration routes and timing of treatment in a pre-clinical model of BPD...
November 10, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28948165/expression-and-role-of-oct3-4-in-injury-repair-process-of-rat-alveolar-epithelium-after-5-fu-treatment
#5
Wen-Ya Li, Xu-Lv Ye, Xin-Shan Jia, Lan-Ling Jia
OBJECTIVE: We aimed to investigate how the embryonic stem cell-related gene Oct3/4 changes during the injury-repair process of distal pulmonary epithelium induced by 5-fluorouracil (5-Fu). METHODS: We have developed the lung injury model induced by 5-Fu and observed the dynamic changes of Oct3/4 by indirect immunofluorescence, Western blot, and quantitative real-time PCR. Immunofluorescence double staining was used to compare the positions of Oct3/4(+) cells and other reported alveolar epithelial stem cells...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28791807/proceedings-regenerative-medicine-for-lung-diseases-a-cirm-workshop-report
#6
Lisa C Kadyk, Natalie D DeWitt, Brigitte Gomperts
The mission of the California Institute of Regenerative Medicine (CIRM) is to accelerate treatments to patients with unmet medical needs. In September 2016, CIRM sponsored a workshop held at the University of California, Los Angeles to discuss regenerative medicine approaches for treatment of lung diseases, and to identify the challenges remaining for advancing such treatments to the clinic and market approval. Workshop participants discussed current preclinical and clinical approaches to regenerative medicine in the lung, as well as the biology of lung stem cells and the role of stem cells in the etiology of various lung diseases...
August 9, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28783251/safety-and-efficacy-of-allogeneic-lung-spheroid-cells-in-a-mismatched-rat-model-of-pulmonary-fibrosis
#7
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...
October 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28780147/stem-cells-in-pulmonary-disease-and-regeneration
#8
REVIEW
Rohan R Nadkarni, Soumeya Abed, Jonathan S Draper
The epithelial cells lining the mammalian lung are subjected to constant interaction with the external environment, necessitating robust regeneration strategies to deal with cell loss due to natural turnover or damage arising from inhaled agents or disease. Since lung epithelial function extends beyond respiratory gas exchange to include roles such as immune defense and mucociliary clearance, a diverse complement of epithelial cell types exists that are regionally distributed along the respiratory tree and extensive surface area of the alveolar interface...
April 2018: Chest
https://www.readbyqxmd.com/read/28666430/derivation-of-therapeutic-lung-spheroid-cells-from-minimally-invasive-transbronchial-pulmonary-biopsies
#9
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/28545380/from-stem-cell-biology-to-the-treatment-of-lung-diseases
#10
Dorina Esendagli, Aysen Gunel-Ozcan
BACKGROUND: The exposure of lung to noxious agents or gasses leads to injury, which further enhances repair mechanisms by promoting the proliferation and differentiation of lung stem cells. These cells could help preserve the anatomical structure and the function of the organ. Unfortunately in many lung diseases, 'this scenario' is changed and injury progresses despite repair mechanisms or conventional treatment. OBJECTIVE: This review summarizes the research on lung stem cells by giving an overview of the biology, function, niches and signaling that play role in lung stem cells and further of the regeneration of the lung...
2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28501476/endothelial-cells-are-not-required-for-specification-of-respiratory-progenitors
#11
Jamie A Havrilak, Kristin R Melton, John M Shannon
Crosstalk between mesenchymal and epithelial cells influences organogenesis in multiple tissues, such as lung, pancreas, liver, and the nervous system. Lung mesenchyme comprises multiple cell types, however, and precise identification of the mesenchymal cell type(s) that drives early events in lung development remains unknown. Endothelial cells have been shown to be required for some aspects of lung epithelial patterning, lung stem cell differentiation, and regeneration after injury. Furthermore, endothelial cells are involved in early liver and pancreas development...
July 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28479114/bronchopulmonary-dysplasia-where-have-all-the-stem-cells-gone-origin-and-potential-function-of-resident-lung-stem-cells
#12
REVIEW
Marius Alexander Möbius, Bernard Thébaud
Celebrating its 50th anniversary in 2017, bronchopulmonary dysplasia (BPD)-the chronic lung disease of prematurity that follows ventilator and oxygen therapy for acute respiratory failure-remains the most frequent complication of extreme prematurity. Survival of premature infants born at increasingly earlier stages of gestation has made the prevention of lung injury increasingly challenging. BPD is postulated to be a misdirection of many functions in the developing lung, including growth factor signalling and matrix as well as cellular composition, resulting in impaired alveolar and lung vascular growth...
November 2017: Chest
https://www.readbyqxmd.com/read/28326803/when-is-an-alveolar-type-2-cell-an-alveolar-type-2-cell-a-conundrum-for-lung-stem-cell-biology-and-regenerative-medicine
#13
REVIEW
Michael F Beers, Yuben Moodley
Generating mature, differentiated, adult lung cells from pluripotent cells, such as induced pluripotent stem cells and embryonic stem cells, offers the hope of both generating disease-specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung-regenerative medicine, several groups have developed and reported on protocols using defined media, coculture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors...
July 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27825158/regeneration-of-the-aging-lung-a-mini-review
#14
REVIEW
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...
2017: Gerontology
https://www.readbyqxmd.com/read/27713058/organogenesis-of-adult-lung-in-a-dish-differentiation-disease-and-therapy
#15
REVIEW
Jinwook Choi, Elhadi Iich, Joo-Hyeon Lee
The remarkable regenerative capacity of the lung suggests that stem cells could be of therapeutic importance in diverse lung diseases; however, the successful exploitation of lung stem cell biology has long been hampered by our inability to maintain and expand adult lung stem cells while retaining their multi-lineage potential in vitro. Recently, advances in our understanding of stem cell niches and the role of key signalling modulators in controlling stem cell maintenance and differentiation have fuelled the development of new in vitro three-dimensional (3D) culture technologies that sustain the stem cell-driven formation of near-physiological, self-organizing structures called organoids...
December 15, 2016: Developmental Biology
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
#16
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
https://www.readbyqxmd.com/read/27524796/stem-cells-in-lung-injury-and-repair
#17
REVIEW
Felicia Chen, Alan Fine
In this review, we summarize the recent literature on the biology of endogenous stem cells in adult lung injury repair. We focus on in vivo studies in mice with an emphasis on data generated using cell-specific Cre-dependent lineage-tracing systems. These studies provide new information on the identification of lung stem cells, their hierarchical relationships, the plasticity of their behavior in different types of injury, and the molecular signals that control their fates. Although most of this work has been on epithelial hierarchies, we expect that further development of robust genetic tools will foster meaningful investigations into how nonepithelial cell populations are controlled during lung injury repair in adults...
October 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27322618/influenza-virus-infects-epithelial-stem-progenitor-cells-of-the-distal-lung-impact-on-fgfr2b-driven-epithelial-repair
#18
Jennifer Quantius, Carole Schmoldt, Ana I Vazquez-Armendariz, Christin Becker, Elie El Agha, Jochen Wilhelm, Rory E Morty, István Vadász, Konstantin Mayer, Stefan Gattenloehner, Ludger Fink, Mikhail Matrosovich, Xiaokun Li, Werner Seeger, Juergen Lohmeyer, Saverio Bellusci, Susanne Herold
Influenza Virus (IV) pneumonia is associated with severe damage of the lung epithelium and respiratory failure. Apart from efficient host defense, structural repair of the injured epithelium is crucial for survival of severe pneumonia. The molecular mechanisms underlying stem/progenitor cell mediated regenerative responses are not well characterized. In particular, the impact of IV infection on lung stem cells and their regenerative responses remains elusive. Our study demonstrates that a highly pathogenic IV infects various cell populations in the murine lung, but displays a strong tropism to an epithelial cell subset with high proliferative capacity, defined by the signature EpCamhighCD24lowintegrin(α6)high...
June 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27197183/mir-17-92-p38%C3%AE-dysregulation-enhances-wnt-signaling-and-selects-lgr6-cancer-stem-like-cells-during-lung-adenocarcinoma-progression
#19
Anna Guinot, Feride Oeztuerk-Winder, Juan-Jose Ventura
Defining the molecular and cellular roots of lung cancer relapse after initial treatment remains an imperative to improve survival. Here we report that the lung stem cell marker Lgr6 becomes enriched in non-small cell lung cancer (NSCLC) cells during malignant progression. Lgr6(+) NSCLC cells displayed self-renewal and differentiation properties along with a higher tumorigenic potential. Mechanistic investigations suggested that a defective repression of the miR-17-92 gene cluster was responsible for evolution of a selection for outgrowth of Lgr6(+) NSCLC cells...
July 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27107715/regeneration-of-the-lung-lung-stem-cells-and-the-development-of-lung-mimicking-devices
#20
REVIEW
Kim A A Schilders, Evelien Eenjes, Sander van Riet, André A Poot, Dimitrios Stamatialis, Roman Truckenmüller, Pieter S Hiemstra, Robbert J Rottier
Inspired by the increasing burden of lung associated diseases in society and an growing demand to accommodate patients, great efforts by the scientific community produce an increasing stream of data that are focused on delineating the basic principles of lung development and growth, as well as understanding the biomechanical properties to build artificial lung devices. In addition, the continuing efforts to better define the disease origin, progression and pathology by basic scientists and clinicians contributes to insights in the basic principles of lung biology...
April 23, 2016: Respiratory Research
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