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Stem cell and ARDS

Michael A Matthay, Shibani Pati, Jae-Woo Lee
Several experimental studies have provided evidence that bone-marrow derived mesenchymal stem (stromal) cells (MSC) may be effective in treating critically ill surgical patients who develop traumatic brain injury, acute renal failure, or the acute respiratory distress syndrome. There is also preclinical evidence that MSC may be effective in treating sepsis-induced organ failure, including evidence that MSC have anti-microbial properties. This review considers preclinical studies with direct relevance to organ failure following trauma, sepsis or major infections that apply to critically ill patients...
November 26, 2016: Stem Cells
Yaoqin Hu, Chaojin Qin, Guoping Zheng, Dengming Lai, Huikang Tao, Yan Zhang, Guanguan Qiu, Menghua Ge, Lanfang Huang, Lina Chen, Baoli Cheng, Qiang Shu, Jianguo Xu
Both bone marrow and adipose-derived mesenchymal stem cells (ASCs) have immunomodulatory effects. The goal of this study was to determine whether ASCs-educated macrophages could directly ameliorate LPS-induced systemic response in a mouse model. Mouse peritoneal macrophages were cocultured with ASCs in a Transwell system for 2 days to educate macrophages. Mice were divided into 5 groups: control, LPS, LPS + ASCs, LPS + untreated macrophages, and LPS + educated macrophages. Educated macrophages decreased lung inflammation, weight loss, pulmonary edema, and inflammatory cytokine response...
2016: Mediators of Inflammation
Shirley Hsin-Ju Mei, Claudia Dos Santos, Duncan Stewart
Given the failure of pharmacological interventions in acute respiratory distress syndrome (ARDS), researchers have been actively pursuing novel strategies to treat this devastating, life-threatening condition commonly seen in the Intensive Care Unit. There has been considerable research on harnessing the reparative properties of stem and progenitor cells to develop more effective therapeutic approaches for respiratory diseases with limited treatment options like ARDS. This review will discuss the preclinical literature on the use of stem and progenitor cell therapy and cell-based gene therapy for the treatment of preclinical animal models of acute lung injury (ALI)...
August 16, 2016: Human Gene Therapy
Thanathom Chailangkarn, Cleber A Trujillo, Beatriz C Freitas, Branka Hrvoj-Mihic, Roberto H Herai, Diana X Yu, Timothy T Brown, Maria C Marchetto, Cedric Bardy, Lauren McHenry, Lisa Stefanacci, Anna Järvinen, Yvonne M Searcy, Michelle DeWitt, Wenny Wong, Philip Lai, M Colin Ard, Kari L Hanson, Sarah Romero, Bob Jacobs, Anders M Dale, Li Dai, Julie R Korenberg, Fred H Gage, Ursula Bellugi, Eric Halgren, Katerina Semendeferi, Alysson R Muotri
Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells...
August 18, 2016: Nature
Muneyoshi Kimura, Hideki Araoka, Atsushi Yoshida, Hisashi Yamamoto, Masahiro Abe, Yuki Okamoto, Mitsuhiro Yuasa, Daisuke Kaji, Kosei Kageyama, Aya Nishida, Kazuya Ishiwata, Shinsuke Takagi, Go Yamamoto, Yuki Asano-Mori, Naoyuki Uchida, Akira Hishinuma, Koji Izutsu, Atsushi Wake, Shuichi Taniguchi, Akiko Yoneyama
BACKGROUND: Breakthrough viridans streptococcal bacteremia (VSB) in patients with hematological malignancy receiving levofloxacin prophylaxis is a major blood stream infection (BSI) occurring during febrile neutropenia. However, clinical data focused on VSB in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are lacking. METHODS: The medical records of allo-HSCT recipients who received oral levofloxacin prophylaxis between January 2011 and August 2013 at Toranomon Hospital were reviewed to evaluate breakthrough VSB...
2016: BMC Infectious Diseases
Fernanda F Cruz, Daniel J Weiss, Patricia R M Rocco
INTRODUCTION: Despite progress in understanding the pathophysiology of the acute respiratory distress syndrome (ARDS), it remains a devastating clinical disorder associated with high mortality rates, and those who survive can experience significant long-term morbidity. Recent advances in the management of ARDS have mostly been achieved in supportive care, including the use of protective mechanical ventilation, neuromuscular blocking agents, prone positioning, and conservative fluid strategies...
August 4, 2016: Expert Opinion on Biological Therapy
Shahd Horie, John G Laffey
Acute respiratory distress syndrome (ARDS) causes respiratory failure, which is associated with severe inflammation and lung damage and has a high mortality and for which there is no therapy. Mesenchymal stromal/stem cells (MSCs) are adult multi-progenitor cells that can modulate the immune response and enhance repair of damaged tissue and thus may provide a therapeutic option for ARDS. MSCs demonstrate efficacy in diverse in vivo models of ARDS, decreasing bacterial pneumonia and ischemia-reperfusion-induced injury while enhancing repair following ventilator-induced lung injury...
2016: F1000Research
Jurjan Aman, Ester M Weijers, Geerten P van Nieuw Amerongen, Asrar B Malik, Victor W M van Hinsbergh
Despite considerable progress in the understanding of endothelial barrier regulation and the identification of approaches that have the potential to improve endothelial barrier function, no drug- or stem cell-based therapy is presently available to reverse the widespread vascular leak that is observed in acute respiratory distress syndrome (ARDS) and sepsis. The translational gap suggests a need to develop experimental approaches and tools that better mimic the complex environment of the microcirculation in which the vascular leak develops...
August 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Yi Yang, Shuling Hu, Xiuping Xu, Jinze Li, Airan Liu, Jibin Han, Songqiao Liu, Ling Liu, Haibo Qiu
Recently, mesenchymal stem cells (MSC) have been proved to be beneficial in acute respiratory distress syndrome (ARDS). Vascular endothelial growth factor (VEGF) is an important angiogenesis factor that MSC release. However, the precise role of VEGF-expressing character of MSC in the MSC treatment for ARDS remains obscure. Here, we firstly knocked down the gene VEGF in MSC (MSC-ShVEGF) with lentiviral transduction. Then we injected the MSC-ShVEGF to rats with lipopolysaccharide-induced acute lung injury (ALI) via the tail vein...
2016: Mediators of Inflammation
Yuben Moodley, Marian Sturm, Kathryn Shaw, Chiko Shimbori, Dino B A Tan, Martin Kolb, Ruth Graham
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a major cause of global morbidity and mortality. Mesenchymal stem cells (MSC) have shown promise in treating inflammatory lung conditions. We hypothesised that human MSC (hMSC) can improve ALI/ARDS through their anti-inflammatory actions. We subjected pigs (n=6) to intravenous oleic acid (OA) injury, ventilation and hMSC infusion, while the controls (n=5) had intravenous OA, ventilation and an infusion vehicle control. hMSC were infused 1h after the administration of OA...
July 2016: Stem Cell Research
Jibin Han, Xiaomin Lu, Lijuan Zou, Xiuping Xu, Haibo Qiu
Mesenchymal stem cells (MSCs) represent a promising approach for the treatment of acute respiratory distress syndrome (ARDS). However, their low efficiency in homing to injured lung tissue limits their therapeutic effect. Prostaglandin E2 (PGE2) biosynthesis substantially enhances the inflammatory response of the tissue. Moreover, it also facilitates the migration of MSCs by activating the E-prostanoid 2 (EP2) receptor in vitro. Given these observations, it would seem reasonable that PGE2 might act as a chemokine to promote the migration of MSCs through activation of the EP2 receptor...
August 2016: Human Gene Therapy
Shuling Hu, Jinze Li, Xiuping Xu, Airan Liu, Hongli He, Jingyuan Xu, Qihong Chen, Songqiao Liu, Ling Liu, Haibo Qiu, Yi Yang
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening condition in critically ill patients. Recently, we have found that mesenchymal stem cells (MSC) improved the permeability of human lung microvascular endothelial cells by secreting hepatocyte growth factor (HGF) in vitro. However, the properties and functions of MSC may change under complex circumstances in vivo. Here, we sought to determine the role of the HGF-expressing character of MSC in the therapeutic effects of MSC on ARDS in vivo...
2016: Stem Cell Research & Therapy
Francisco Espinoza, Felipe Aliaga, Patricia Luz Crawford
Development of innovative therapies in intensive care medicine is particularly important since diseases as sepsis, acute respiratory distress syndrome (ARDS) and acute renal injury (AKI) have an elevated morbidity and mortality in spite of current gold-standard approaches. Mesenchymal stem cells (MSC) may have a promising role due to their properties in immunomodulation, tissue reparation and microbial clearance. Preclinical data and results of a systematic review of PubMed, PMC and have been included to review the role of MSC therapy in sepsis, ARDS and AKI...
February 2016: Revista Médica de Chile
Megan V Jackson, Thomas J Morrison, Declan F Doherty, Daniel F McAuley, Michael A Matthay, Adrien Kissenpfennig, Cecilia M O'Kane, Anna D Krasnodembskaya
Mesenchymal stromal cells (MSC) have been reported to improve bacterial clearance in preclinical models of Acute Respiratory Distress Syndrome (ARDS) and sepsis. The mechanism of this effect is not fully elucidated yet. The primary objective of this study was to investigate the hypothesis that the antimicrobial effect of MSC in vivo depends on their modulation of macrophage phagocytic activity which occurs through mitochondrial transfer. We established that selective depletion of alveolar macrophages (AM) with intranasal (IN) administration of liposomal clodronate resulted in complete abrogation of MSC antimicrobial effect in the in vivo model of Escherichia coli pneumonia...
August 2016: Stem Cells
F-B Liu, Q Lin, Z-W Liu
OBJECTIVE: We sought to determine whether normal human umbilical cord mesenchymal stem cells and apoptotic human umbilical cord mesenchymal stem cells play any role in the lung repair following bleomycin-induced lung injury in rat models. MATERIALS AND METHODS: Umbilical cord mesenchymal stem cells were obtained from the umbilical cord following caesarian section from healthy normal babies. Plasmin deprivation method was used for culture of human umbilical cord mesenchymal stem cells and flow cytometry was used to identify cell surface antigen and activity of stem cells and apoptosis...
March 2016: European Review for Medical and Pharmacological Sciences
J N Gonzales, R Lucas, A D Verin
Acute Respiratory Distress Syndrome (ARDS) is a severe lung inflammatory disorder with a 30-50% mortality. Sepsis and pneumonia are the leading causes of ARDS. On the cellular level there is pulmonary capillary endothelial cell permeability and fluid leakage into the pulmonary parenchyma, followed by neutrophils, cytokines and an acute inflammatory response. When fluid increases in the interstitium then the outward movement continues and protein rich fluid floods the alveolar spaces through the tight junctions of the epithelial cells...
June 4, 2015: Austin Journal of Vascular Medicine
Shahd Horie, Claire Masterson, James Devaney, John G Laffey
PURPOSE OF REVIEW: Acute respiratory distress syndrome (ARDS) is a devastating disease process with a 40% mortality rate, and for which there is no therapy. Stem cells are an exciting potential therapy for ARDS, and are currently the subject of intensive ongoing research efforts. We review data concerning the therapeutic promise of cell-based therapies for ARDS. RECENT FINDINGS: Recent experimental studies suggest that cell-based therapies, particularly mesenchymal stem/stromal cells (MSCs), endothelial progenitor cells, and embryonic or induced pluripotent stem cells all offer considerable promise for ARDS...
February 2016: Current Opinion in Critical Care
Jie Chen, Yanqin Li, Haojie Hao, Chonghui Li, Yu Du, Ye Hu, Jian Li, Zhixin Liang, Chunsun Li, Jiejie Liu, Liangan Chen
BACKGROUND/AIMS: Mesenchymal stem cell (MSC) based therapies may be useful for treating acute respiratory distress syndrome (ARDS), but the underlying mechanisms are incompletely understood. We investigated the impact of human umbilical cord Wharton's jelly-derived MSC (hUC-MSC) secreted factors on alveolar epithelial cells under septic conditions and determined the relevant intracellular signaling pathways. METHODS: Human alveolar epithelial cells (AEC) and primary human small airway epithelial cells (SAEC) were subjected to lipopolysaccharide (LPS) with or without the presence of hUC-MSC-conditioned medium (CM)...
2015: Cellular Physiology and Biochemistry
Debasmita Roy, David Michaelson, Tsivia Hochman, Anthony Santella, Zhirong Bao, Judith D Goldberg, E Jane Albert Hubbard
Many organisms accumulate a pool of germline stem cells during development that is maintained in later life. The dynamics of establishment, expansion and homeostatic maintenance of this pool are subject to both developmental and physiological influences including the availability of a suitable niche microenvironment, nutritional status, and age. Here, we investigated the dynamics of germline proliferation during stages of expansion and homeostasis, using the C. elegans germ line as a model. The vast majority of germ cells in the proliferative zone are in interphase stages of mitosis (G1, S, G2) rather than in the active mitotic (M) phase...
January 1, 2016: Developmental Biology
Ce Yang, Xuetao Yang, Juan Du, Haiyan Wang, Haisheng Li, Ling Zeng, Wei Gu, Jianxin Jiang
BACKGROUND: The treatment of acute respiratory distress syndrome (ARDS), most commonly seen during the organ dysfunction remains unsatisfied. Presently, the stem/progenitor cell-based endogenous repair has been aroused attention enormously. This report investigated the effects of retinoic acid (RA) plus simvastatin (SS) with respect to dynamics of lung repair cells as well as to elucidate the underlying mechanism. MATERIALS AND METHODS: The experimental Sprague-Dawley rats were divided randomly into normal control (control), sham operated (sham), ARDS, ARDS +  vehicle and ARDS + RA + SS groups...
November 11, 2015: Respiratory Research
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