Abstract:
RATIONALE:Recent studies have suggested that both embryonic stem cells and adult bone marrow stem cells can participate in the regeneration and repair of diseased adult organs, including the lungs. However, the extent of airway epithelial remodeling with adult marrow stem cells is low, and there are no available in vivo data with embryonic stem cells. Human umbilical cord blood contains both hematopoietic and nonhematopoietic stem cells, which have been used clinically as an alternative to bone marrow transplantation for hematologic malignancies and other diseases. OBJECTIVES:We hypothesized that human umbilical cord blood stem cells might be an effective alternative to adult bone marrow and embryonic stem cells for regeneration and repair of injured airway epithelium. METHODS:Human cord blood was obtained from normal deliveries at the University of Vermont. Cultured plastic adherent cells were characterized as mesenchymal stem cells (MSCs) by flow cytometry and differentiation assays. Cord blood-derived MSCs (CB-MSCs) were cultured in specialized airway growth media or with specific growth factors, including keratinocyte growth factor and retinoic acid. mRNA and protein expression were analyzed with PCR and immunofluorescent staining. CB-MSCs were systematically administered to immunotolerant, nonobese diabetic/severe combined immunodeficiency (NOD-SCID) mice. Lungs were analyzed for presence of human cells. MEASUREMENTS AND MAIN RESULTS:When cultured in specialized airway growth media or with specific growth factors, CB-MSCs differentially expressed Clara cell secretory protein (CCSP), cystic fibrosis transmembrane conductance regulator (CFTR), surfactant protein C, and thyroid transcription factor-1 mRNA, and CCSP and CFTR protein. Furthermore, CB-MSCs were easily transduced with recombinant lentiviral vectors to express human CFTR. After systemic administration to immunotolerant, NOD-SCID, mice, rare cells were found in the airway epithelium that had acquired cytokeratin and human CFTR expression. CONCLUSIONS:CB-MSCs appear to be comparable to MSCs obtained from adult bone marrow in ability to express phenotypic markers of airway epithelium and to participate in airway remodeling in vivo.
journal_name
Am J Respir Crit Care Medauthors
Sueblinvong V,Loi R,Eisenhauer PL,Bernstein IM,Suratt BT,Spees JL,Weiss DJdoi
10.1164/rccm.200706-859OCsubject
Has Abstractpub_date
2008-04-01 00:00:00pages
701-11issue
7eissn
1073-449Xissn
1535-4970pii
200706-859OCjournal_volume
177pub_type
杂志文章abstract:BACKGROUND:Mild obstructive sleep apnea (OSA) is a highly prevalent disorder in adults; however, whether mild OSA has significant neurocognitive and cardiovascular complications is uncertain. OBJECTIVES:The specific goals of this Research Statement are to appraise the evidence regarding whether long-term adverse neuro...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/rccm.201602-0361ST
更新日期:2016-05-01 00:00:00
abstract::The effects of conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFO) on intraalveolar expression of the tumor necrosis factor-alpha (TNF-alpha) gene were studied in surfactant-depleted rabbits. After lung lavage with saline, 13 rabbits were administered either CMV (n = 6) or HFO (n...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.1.9607072
更新日期:1997-07-01 00:00:00
abstract:RATIONALE:Lung allografts are prone to reperfusion injury and acute rejection, which, in addition to infiltrating lymphocytes, are accompanied by neutrophil infiltration and neutrophil-associated oxidative stress. Indoleamine 2,3-dioxygenase (IDO) is a unique cytosolic enzyme that possesses T-cell-suppressive and antio...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200509-1413OC
更新日期:2006-03-01 00:00:00
abstract:RATIONALE:Severe asthma is a major public health issue throughout the world. Increased bronchial smooth muscle (BSM) mass, a characteristic feature of airway remodeling in severe asthma, is associated with resistance to high-intensity treatment and poor prognosis. In vitro, the Ca(2+)-channel blocker gallopamil decreas...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1164/rccm.201410-1874OC
更新日期:2015-04-15 00:00:00
abstract::The inheritance of asthma, evident from its high family concordance, is not well understood. To investigate whether asthma may be inherited through a major gene with two alleles, segregation analyses were conducted in 3,369 individuals from 906 nuclear families enrolled, without selection, in a longitudinal study of r...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.154.1.8680670
更新日期:1996-07-01 00:00:00
abstract:RATIONALE:Allergic asthma is characterized by reversible airway obstruction, lung inflammation, and airway hyperresponsiveness (AHR). Previous studies using leukotriene B(4) (LTB(4)) receptor 1-deficient mice and adoptive transfer experiments have suggested that LTB(4) plays a role in lung inflammation and AHR. OBJECT...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200807-1158OC
更新日期:2010-05-01 00:00:00
abstract::Studies have shown evidence of significant parent-offspring and sibling correlation in FEV1, but familial aggregation of decline of FEV1 over time has not been reported. Our study population comprised 392 families enrolled in the Tucson Epidemiological Study of Airway Obstructive Diseases. Subjects were older than 18 ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.7.2010051
更新日期:2001-10-01 00:00:00
abstract::Effects of nitric oxide (NO) and aerosolized terbutaline inhalation on ventilation-perfusion (VA/Q) distributions were determined during methacholine-induced bronchoconstriction in nine mechanically ventilated pigs. Animals inhaled, in random order, zero, 20, and 80 parts per million (ppm) of NO or aerosolized terbuta...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.1.7812540
更新日期:1995-01-01 00:00:00
abstract::Several studies have found that sleep deprivation reduces the hypercapnic ventilatory response (HCVR). Such results may have been affected by uncontrolled activities or environmental influences during the sleep deprivation period. The current study determined the "pure" effect of sleep deprivation on respiratory contr...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.4.9906026
更新日期:2000-04-01 00:00:00
abstract::Obstructive sleep-disordered breathing is associated with cardiovascular disease in adults, and elevated C-reactive protein (CRP) has been proposed as a link between the two disorders. We hypothesized that children with sleep-disordered breathing have higher CRP values than do control subjects. CRP was measured in 39 ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200407-928OC
更新日期:2005-02-01 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) is a condition in which continuous bronchodilation may have clinical advantages. This study evaluated salmeterol, a beta-agonist bronchodilator with a duration of action substantially longer than that of short-acting beta-agonists, compared with ipratropium, an anticholiner...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1164/ajrccm.163.5.9903053
更新日期:2001-04-01 00:00:00
abstract::The lobar and cephalocaudal distribution of aerated and nonaerated lung and of PEEP-induced alveolar recruitment is unknown in acute lung injury (ALI). Dimensions of the lungs and volumes of aerated and nonaerated parts of each pulmonary lobe were measured using a computerized tomographic quantitative analysis and com...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.5.9802003
更新日期:1998-11-01 00:00:00
abstract::In patients with chronic obstructive pulmonary disease (COPD) the intensity of aerobic training is limited by dyspnea. Improving strength of the inspiratory muscles could enhance aerobic exercise training by reducing exercise-related dyspnea. We examined effects of home-based inspiratory muscle training (IMT) and cycl...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.160.2.9804067
更新日期:1999-08-01 00:00:00
abstract::While signal transducer and activator of transcription protein 6 (STAT6) is important in interleukin-4 (IL-4)-induced commitment of CD4(+) T cells to the T helper cell, type 2 (Th2) phenotype and IgE isotype switching in B cells, its role in other IL-4-mediated events and their impact upon the allergic response is les...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.160.4.9809065
更新日期:1999-10-01 00:00:00
abstract::Although hematopoietic stem cell transplantation (HSCT) can be curative in patients with certain malignancies, survival is poor if the recipient becomes critically ill. This prospective study examined the outcomes of 115 consecutive HSCT patients admitted to the medical intensive care unit (MICU) of a tertiary cancer ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.3.9711076
更新日期:1998-09-01 00:00:00
abstract::Two patients receiving low dose methotrexate, one with rheumatoid arthritis and the other with pityriasis rubra pilaris, developed disseminated histoplasmosis and Mycobacterium avium intracellulare pneumonia, respectively. Twenty-three cases of opportunistic infection in patients receiving low dose methotrexate have b...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm.150.1.8025760
更新日期:1994-07-01 00:00:00
abstract::Previous studies reported linkage between maternally inherited atopy and the beta subunit of the high affinity IgE receptor (Fc epsilon RI-beta) located on chromosome 11q13. We have investigated 45 Italian families with atopic asthmatic children, for a total of 213 subjects, including 148 patients. Genotyping was carr...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.5.8630620
更新日期:1996-05-01 00:00:00
abstract::In 35 patients fulfilling the criteria of systemic inflammatory response syndrome (SIRS) of infectious origin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), tumor necrosis factor-soluble receptor (TNF-sR), and interleukin-12 (IL-12), C-reactive protein (CRP) levels and the Acute Physiology, and Chroni...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.3.9607131
更新日期:1997-09-01 00:00:00
abstract::At present there is some indirect evidence for increased nocturnal inflammation in patients suffering from nocturnal asthma: 1. Circulating eosinophil numbers and activation, as reflected by increased levels of ECP and EDN and low-density eosinophils, are increased at night. 2. Circulating histamine levels are increas...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm/150.5_Pt_2.S83
更新日期:1994-11-01 00:00:00
abstract:RATIONALE:Defective efferocytosis (phagocytic clearance of apoptotic cells) in the airway may perpetuate inflammation via secondary necrosis in chronic obstructive pulmonary disease (COPD). We have previously reported that low-dose azithromycin improved alveolar macrophage (AM) phagocytic function in vitro. OBJECTIVES...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.200711-1666OC
更新日期:2008-07-15 00:00:00
abstract::The severity of asthma can be graded from mild intermittent to severe persistent. Airway inflammation is a feature of persistent asthma. We compared several markers of inflammation in mucosal biopsies and bronchoalveolar lavage fluid (BAL fluid) from 12 healthy control subjects, 24 patients with intermittent asthma, a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.2.96-08040
更新日期:1998-02-01 00:00:00
abstract:RATIONALE:T-bet (TBX21 or T-box 21) is a critical regulator of T-helper 1 lineage commitment and IFN-gamma production. Knockout mice lacking T-bet develop airway hyperresponsiveness (AHR) to methacholine, peribronchial eosinophilic and lymphocytic inflammation, and increased type III collagen deposition below the bronc...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200503-505OC
更新日期:2006-01-01 00:00:00
abstract::Alkaline phosphatase (ALP) in lung lavage fluids is a marker of tissue damage and type II cell proliferation. Type II pneumocytes are extensively involved in fibrosis. The aim of our study was to verify whether local ALP activity can be held as a marker of fibrosis in chronic interstitial lung disorders. ALP was deter...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.1.9001320
更新日期:1997-01-01 00:00:00
abstract:RATIONALE:Immunophenotypes of antiviral responses, and their relationship with asthma, allergy, and lower respiratory tract infections, are poorly understood. OBJECTIVES:We characterized multiple cytokine responses of peripheral blood mononuclear cells to rhinovirus stimulation, and their relationship with clinical ou...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201708-1762OC
更新日期:2018-05-15 00:00:00
abstract::A 21-yr-old man with multiple pulmonary AV fistulae presented with moderate hypoxemia with chronic hyperventilation, which continued even after sufficient oxygenation by 100% O2 inhalation. The infusion of aminophylline, an adenosine receptor blocker, not only increased PaCO2 from 35 to 39 mm Hg but also depressed the...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm.150.6.7952640
更新日期:1994-12-01 00:00:00
abstract::The role of nitric oxide (NO) in the host-defense against human tuberculosis (TB) is controversial. Although experimental evidence indicates that NO may play an important role in controlling TB, its expression in human tuberculous lungs has not been systematically characterized. We therefore investigated the expressio...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2201023
更新日期:2002-07-15 00:00:00
abstract::Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation.Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (≥12 yr) and a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201906-1227OC
更新日期:2020-01-15 00:00:00
abstract::A protective role for dietary antioxidants in asthma has been proposed. However, epidemiological evidence to implicate antioxidant vitamins is weak, and data on the role of flavonoid-rich foods and antioxidant trace elements are lacking. We carried out a population-based case-control study in South London, UK, to inve...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.10.2104061
更新日期:2001-11-15 00:00:00
abstract::To investigate the annual decline of lung function in subjects with self-reported asthma, we analyzed data from a longitudinal epidemiologic study. The Copenhagen City Heart Study. The study sample consisted of 10,952 subjects (4,824 men), 20 to 90 yr of age, randomly selected from the city of Copenhagen followed over...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.150.3.8087330
更新日期:1994-09-01 00:00:00
abstract::Asthma is a chronic inflammatory disease that persists even during adequate therapy and asymptomatic episodes. We questioned whether "silent" chronic allergen exposure can induce and maintain airway inflammation and whether this still occurs during regular treatment with inhaled steroids. Twenty-six patients with hous...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/rccm.2112097
更新日期:2002-08-01 00:00:00