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stem cell therapy for Acute lung injury

Jing Zhang, Yiru Shao, Daikun He, Lin Zhang, Guoxiong Xu, Jie Shen
: An increase in epithelial cell permeability has been proposed to contribute to phosgene-induced acute lung injury (ALI). However, no specific and effective means for blocking increases in permeability are currently available. Cell-based therapy using bone marrow-derived mesenchymal stem cells (MSCs) is an attractive new approach. Canonical wnt/β-catenin signaling has been demonstrated to contribute to both epithelial cell injury and repair mechanisms in ALI. The goal of our study was to determine the effects of MSCs on epithelial permeability in phosgene-induced ALI in Sprague-Dawley (SD) rats and identify changes in major components of the wnt3a/β-catenin signaling pathway during this process...
October 2016: Inhalation Toxicology
Diana Klein, Jennifer Steens, Alina Wiesemann, Florian Christoph Schulz, Farnusch Kaschani, Katharina Roeck, Masahiro Yamaguchi, Florian Wirsdörfer, Markus Kaiser, Jens Fischer, Martin Stuschke, Verena Jendrossek
AIMS: Radiation-induced normal tissue toxicity is closely linked to endothelial cell (EC) damage and dysfunction (acute effects). However, the underlying mechanisms of radiation-induced adverse late effects with respect to the vascular compartment remain elusive and no causative radioprotective treatment is available to date. RESULTS: The importance of injury to EC for radiation-induced late toxicity in lungs after whole thorax irradiation (WTI) was investigated using a mouse model of radiation-induced pneumopathy...
August 29, 2016: Antioxidants & Redox Signaling
S Chen, X Chen, X Wu, S Wei, W Han, J Lin, M Kang, L Chen
Accumulative evidence demonstrated that mesenchymal stem cell (MSC) engraftment could protect tissue injury from ischemia/reperfusion (I/R). Hepatocyte growth factor (HGF) plays important roles in the cell and tissue repairment and regeneration. Here, we investigated the enhanced effects of HGF-modified MSCs on I/R-induced acute lung injury. Rat bone marrow- derived MSCs were successfully transfected to express HGF. HGF modification did not affect the characteristics of MSCs, and increased MSC viability, and inhibit the proinflammatory phenotype of MSCs in the inflammatory condition...
August 24, 2016: Gene Therapy
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
Micah A Skeens, Jennifer McArthur, Ira M Cheifetz, Christine Duncan, Adrienne G Randolph, Joseph Stanek, Leslie Lehman, Rajinder Bajwa
Veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). Patients with VOD are often critically ill and require close collaboration between transplant physicians and intensivists. We surveyed members of a consortium of pediatric intensive care unit (PICU) and transplant physicians to assess variability in the self-reported approach to the diagnosis and management of VOD. An internet-based self-administered survey was sent to pediatric HSCT and PICU providers from September 2014 to February 2015...
October 2016: Biology of Blood and Marrow Transplantation
Aaron C Spicer, Carolyn S Calfee, Matthew S Zinter, Robinder G Khemani, Victoria P Lo, Mustafa F Alkhouli, Benjamin E Orwoll, Ana L Graciano, Juan P Boriosi, James P Howard, Heidi R Flori, Michael A Matthay, Anil Sapru
OBJECTIVES: Despite declining mortality, acute respiratory distress syndrome is still involved in up to one third of pediatric intensive care deaths. The recently convened Pediatric Acute Lung Injury Consensus Conference has outlined research priorities for the field, which include the need for accurate bedside risk stratification of patients. We aimed to develop a simple yet robust model of mortality risk among pediatric patients with acute respiratory distress syndrome to facilitate the targeted application of high-risk investigational therapies and stratification for enrollment in clinical trials...
October 2016: Pediatric Critical Care Medicine
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
Cameron McDonald-Hyman, Ryan Flynn, Angela Panoskaltsis-Mortari, Nicholas Peterson, Kelli P A MacDonald, Geoffrey R Hill, Leo Luznik, Jonathan S Serody, William J Murphy, Ivan Maillard, David H Munn, Laurence A Turka, John Koreth, Corey S Cutler, Robert J Soiffer, Joseph H Antin, Jerome Ritz, Bruce R Blazar
Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation. In cGVHD, alloreactive T cells and germinal center (GC) B cells often participate in GC reactions to produce pathogenic antibodies. Although regulatory T cells (Tregs) can inhibit GC reactions, Treg numbers are reduced in cGVHD, contributing to cGVHD pathogenesis. Here, we explored 2 means to increase Tregs in cGVHD: interleukin-2/monoclonal antibody (IL-2/mAb) complexes and donor Treg infusions...
August 18, 2016: Blood
Dong Li, Qingshen Liu, Lei Qi, Xiaoyu Dai, Huan Liu, Yunshan Wang
Mesenchymal stem cells (MSCs) are an attractive cellular source for cell‑based therapy, tissue engineering and regenerative medicine. However, the use of MSCs is limited by their low incorporation rate in the graft environment. The majority of cells are lost from the graft within 1 month, due to reduced microenvironment or local inflammation at the graft site. The extracellular matrix (ECM) may assist the survival and expansion of MSCs. The present study aimed to identify an effective approach to increase ECM expression levels by MSCs in order to enhance the therapeutic effect and survival rate of MSCs at the injury site...
August 2016: Molecular Medicine Reports
Xiangde Liu, Qiuhong Fang, Huijung Kim
BACKGROUND: In the last two decades, mesenchymal stem cells (MSCs) have been pre-clinically utilized in the treatment of a variety of kinds of diseases including chronic obstructive pulmonary disease (COPD). The aim of the current study was to systematically review and conduct a meta-analysis on the published pre-clinical studies of MSC administration in the treatment of COPD in animal models. METHODS AND RESULTS: A systematic search of electronic databases was performed...
2016: PloS One
Yunyun Xu, Jian Xiang, He Zhao, Hansi Liang, Jie Huang, Yan Li, Jian Pan, Huiting Zhou, Xueguang Zhang, Jiang Huai Wang, Zhuang Liu, Jian Wang
Human amniotic fluid stem (hAFS) cells have generated a great deal of excitement in cell-based therapies and regenerative medicine. Here, we examined the effect of hAFS cells labeled with dual-polymer-coated UCNP-PEG-PEI nanoparticles in a murine model of acute lung injury (ALI). We observed hAFS cells migration to the lung using highly sensitive in vivo upconversion luminescence (UCL) imaging. We demonstrated that hAFS cells remained viable and retained their ability to differentiate even after UCNP-PEG-PEI labeling...
September 2016: Biomaterials
Barry Weinberger, Rama Malaviya, Vasanthi R Sunil, Alessandro Venosa, Diane E Heck, Jeffrey D Laskin, Debra L Laskin
Most mortality and morbidity following exposure to vesicants such as sulfur mustard is due to pulmonary toxicity. Acute injury is characterized by epithelial detachment and necrosis in the pharynx, trachea and bronchioles, while long-term consequences include fibrosis and, in some instances, cancer. Current therapies to treat mustard poisoning are primarily palliative and do not target underlying pathophysiologic mechanisms. New knowledge about vesicant-induced pulmonary disease pathogenesis has led to the identification of potentially efficacious strategies to reduce injury by targeting inflammatory cells and mediators including reactive oxygen and nitrogen species, proteases and proinflammatory/cytotoxic cytokines...
August 15, 2016: Toxicology and Applied Pharmacology
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
Maneesh Bhargava, Kevin J Viken, Sanjoy Dey, Michael S Steinbach, Baolin Wu, Pratik D Jagtap, LeeAnn Higgins, Angela Panoskaltsis-Mortari, Daniel J Weisdorf, Vipin Kumar, Mukta Arora, Peter B Bitterman, David H Ingbar, Chris H Wendt
Pulmonary complications due to infection and idiopathic pneumonia syndrome (IPS), a noninfectious lung injury in hematopoietic stem cell transplant (HSCT) recipients, are frequent causes of transplantation-related mortality and morbidity. Our objective was to characterize the global bronchoalveolar lavage fluid (BALF) protein expression of IPS to identify proteins and pathways that differentiate IPS from infectious lung injury after HSCT. We studied 30 BALF samples from patients who developed lung injury within 180 days of HSCT or cellular therapy transfusion (natural killer cell transfusion)...
August 2016: Biology of Blood and Marrow Transplantation
Pei-Hsun Sung, Hsin-Ju Chiang, Chih-Hung Chen, Yi-Ling Chen, Tien-Hung Huang, Yen-Yi Zhen, Meng-Wei Chang, Chu-Feng Liu, Sheng-Ying Chung, Yung-Lung Chen, Han-Tan Chai, Cheuk-Kwan Sun, Hon-Kan Yip
UNLABELLED: We hypothesized that combined treatment with autologous adipose-derived mesenchymal stem cell (ADMSC) and ciprofloxacin is superior to ciprofloxacin only in reducing sepsis-induced urogenital organ damage and mortality in rat sepsis syndrome (SS) caused by intrapelvic injection of cecal bacteria (1.0 × 10(4) cells per milliliter; total, 5.0 ml). Male Sprague-Dawley rats (n = 60) equally divided into group 1 (sham-control), group 2 (SS), group 3 (SS-ADMSC [5.0 × 10(5) intravenously at 0...
June 2016: Stem Cells Translational Medicine
Li-Fu Li, Yuh-Lih Chang, Ning-Hung Chen, Chien-Ying Wang, Gwo-Jyh Chang, Meng-Chih Lin, Chih-Hao Chang, Chung-Chi Huang, Jen-Hua Chuang, Yi-Pin Yang, Shih-Hwa Chiou, Yung-Yang Liu
Mechanical ventilation (MV) with hyperoxia is required for providing life support to patients with acute lung injury (ALI). However, MV may cause diaphragm weakness through muscle injury and atrophy, an effect termed ventilator-induced diaphragm dysfunction (VIDD). Src protein tyrosine kinase and class O of forkhead box 1 (FoxO1) mediate acute inflammatory responses and muscle protein degradation induced by oxidative stress. Induced pluripotent stem cells (iPSCs) have been reported to improve hyperoxia-augmented ALI; however, the mechanisms regulating the interactions among VIDD, hyperoxia, and iPSCs are unclear...
July 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
Jingcai Wang, Ying Qin, Xiuju Mi
The study attempted to clarify the protective role of bone marrow-derived mesenchymal stem cell (BMSC) transplantation on LPS-induced acute lung injury (ALI) of rats. BMSC were obtained from bone marrow of rat, cultured and proliferated in vitro. Rats of ALI were established through lipopolysaccharide (LPS) administration. Male rats were allocated to control group, ALI group and BMSC, transplantation group. Rats were sacrificed after BMSC injection after 12h, 24h and 48h. Here we investigated the role of BMSC in LPS-induced alveolar macrophages to further demonstrate the mechanism of BMSC to lung injury...
April 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hong Liu, Yingwei Ding, Yuehui Hou, Guangju Zhao, Yang Lu, Xiao Chen, Qiqi Cai, Guangliang Hong, Qiaomeng Qiu, Zhongqiu Lu
OBJECTIVE: To explore the possible mechanism and protective effect of BMSCs (bone mesenchymal stem cells) carrying superoxide dismutase (SOD) gene on mice with paraquat-induced acute lung injury. METHODS: To establish the cell line of BMSCs bringing SOD gene, lentiviral vector bringing SOD gene was built and co-cultured with BMSCs. A total of 100 BALB/c mice were randomly divided into five groups, namely Control group, poisoning group (PQ group) , BMSCs therapy group (BMSC group) , BMSCs-Cherry therapy group (BMSC-Cherry group) , BMSCs-SOD therapy group (BMSC-SOD group) ...
January 2016: Chinese Journal of Industrial Hygiene and Occupational Diseases
Antoine Monsel, Ying-Gang Zhu, Varun Gudapati, Hyungsun Lim, Jae W Lee
INTRODUCTION: Acute respiratory distress syndrome is a major cause of respiratory failure in critically ill patients. Despite extensive research into its pathophysiology, mortality remains high. No effective pharmacotherapy exists. Based largely on numerous preclinical studies, administration of mesenchymal stem or stromal cell (MSC) as a therapeutic for acute lung injury holds great promise, and clinical trials are currently underway. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved...
July 2016: Expert Opinion on Biological Therapy
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
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