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Journal ArticleDOI

Epithelial cell restoration and regeneration in inflammatory lung diseases

01 Jan 2011-Inflammation and Regeneration (The Japanese Society of Inflammation and Regeneration)-Vol. 31, Iss: 3, pp 290-295
TL;DR: Intratracheal administration of alveolar epithelial type II cells or epithelial progenitor cells has been shown to be effective in animal models of ALI/ARDS and IPF/UIP, suggesting this could be a promising approach to treat inflammatory lung diseases.
Abstract: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is an acute-onset neutrophil-dominant inflammatory lung disease caused by or associated with various illness and injuries. The mortality rate related to this disorder can be as high as 40%. In contrast, idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) is a chronic progressive inflammatory lung disease of unknown etiology, with a mean survival of five years. There are no established treatments for either disease and novel therapies are eagerly desired. Lung epithelial cells were initially discovered to be derived from bone marrow stem cells and progenitor cells. As a result of progress made in regenerative medicine, several types of tissue stem cells and progenitor cells have been identified in the lungs, each of which is involved in tissue repair and regeneration at different levels of the bronchial tree. In terminal bronchioles and alveoli, where lung cells are specifically vulnerable to injuries caused by inflammatory cells, Clara cell-specific protein-positive epithelial cells, including bronchioalveolar stem cells, and a subgroup of alveolar epithelial type II cells, have been identified as lung tissue stem cell and progenitor cell candidates. Intratracheal administration of alveolar epithelial type II cells or epithelial progenitor cells has been shown to be effective in animal models of ALI/ARDS and IPF/UIP. As a novel strategy based on regenerative medicine, this could be a promising approach to treat inflammatory lung diseases.

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Citations
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03 Jun 2010
TL;DR: In this article, human amnion epithelial cells (hAECs), isolated from term placenta and having stem cell-like and antiinflammatory properties, could adopt an alveolar epithelial phenotype and repair a murine model of bleomycin-induced lung injury.
Abstract: Rationale: Chronic lung disease characterized by loss of lung tissue,inflammation, and fibrosis represents a major global health burden. Cellular therapies that could restore pneumocytes and reduce inflammation and fibrosis would be a major advance in management. Objectives: To determine whether human amnion epithelial cells (hAECs), isolated from term placenta and having stem cell–like and antiinflammatory properties, could adopt an alveolar epithelial phenotype and repair a murine model of bleomycin-induced lung injury. Methods: Primary hAECs were cultured in small airway growth medium to determine whether the cells could adopt an alveolar epithelial phenotype. Undifferentiated primary hAECs were also injected parenterally into SCID mice after bleomycin-induced lung injury and analyzed for production of surfactant protein (SP)-A, SP-B, SP-C, and SP-D. Mouse lungs were also analyzed for inflammation and collagen deposition. Measurements and Main Results: hAECs grown in small airway growth medium developed an alveolar epithelial phenotype with lamellar body formation, production of SPs A–D, and SP-D secretion. Although hAECs injected into mice lacked SPs, hAECs recovered from mouse lungs 2 weeks posttransplantation produced SPs. hAECs remained engrafted over the 4-week test period. hAEC administration reduced inflammation in association with decreased monocyte chemoattractant protein-1, tumor necrosis factor-a, IL-1 and -6, and profibrotic transforming growth factor-b in mouse lungs. In addition,lung collagen content was significantly reduced by hAEC treatment as a possible consequence of increased degradation by matrix metalloproteinase-2 and down-regulation of the tissue inhibitors f matrix metalloproteinase-1 and 2. Conclusions: hAECs offer promise as a cellular therapy for alveolar restitution and to reduce lung inflammation and fibrosis.

7 citations

Journal ArticleDOI
TL;DR: It is demonstrated that Tβ4 reduced lung oxidative stress and inflammation following IR and prevented lung tissue injury regardless of timing of administration.
Abstract: Background and objectives: Ischemia–reperfusion (IR) caused by infrarenal abdominal aorta cross-clamping is an important factor in the development of ischemia–reperfusion injury in various distant organs. Materials and Methods: We investigated potential antioxidant/anti-inflammatory effects of thymosin beta 4 (Tβ4) in a rat model of abdominal aortic surgery-induced IR. Tβ4 (10 mg/kg, intravenous (i.v.)) was administered to rats with IR (90-min ischemia, 180-min reperfusion) at two different periods. One group received Tβ4 1 h before ischemia, and the other received 15 min before the reperfusion period. Results: Results were compared to control and non-Tβ4-treated rats with IR. Serum, bronchoalveolar lavage fluid and lung tissue levels of oxidant parameters were higher, while antioxidant levels were lower in the IR group compared to control. IR also increased inflammatory cytokine levels. Tβ4 reverted these parameters in both Tβ4-treated groups compared to the untreated IR group. Conclusions: Since there is no statistical difference between the prescribed results of both Tβ4-treated groups, our study demonstrates that Tβ4 reduced lung oxidative stress and inflammation following IR and prevented lung tissue injury regardless of timing of administration.

5 citations


Cites background from "Epithelial cell restoration and reg..."

  • ...Alveolar epithelial cells are usually identified as targets of inflammatory cells [32]....

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Journal ArticleDOI
12 Nov 2019
TL;DR: The foremost clinical characteristics of RADS are asthma-like symptoms and nonspecific airway hyperresponsiveness, which may be transient or present for a longer period.
Abstract: Reactive Airways Dysfunction Syndrome (RADS) is an abrupt-onset asthmatic disorder of a non-allergy origin [1]. RADS development involves the inhalation of a single high-level irritant exposure [2]. Innate immunity plays a critical role in RADS pathogenesis. Implementation of innate immunity permits the airways to deal with non-microbiological constituents arising after a massive irritant inhalation exposure [3-5]. Allergy, antigenantibody interaction, and actions by immune Th2 lymphocyte are not part of the pathogenetic processes of RADS. Causative agents causing RADS are irritating gases, vapors, aerosols and/or fumes, as well as solvent vapors and acid mists [6,7]. There generally is need for prompt medical assistance within the first 24 hours after the inhalation exposure [8]. The foremost clinical characteristics of RADS are asthma-like symptoms and nonspecific airway hyperresponsiveness, which may be transient or present for a longer period [9,10]. Table 1 presents the diagnostic criteria of RADS [2]. Abstract Reactive Airways Dysfunction Syndrome (RADS) is an abrupt-onset asthmatic disorder of a non-allergy origin. Its mechanism relies on innate immunity that permits the airways to deal with non-microbiological constituents. The massive exposure causes a severe airway injury with ensuing detachment of damaged and dead epithelial cells. There is the release of Molecules of Damage-Associated Molecular Patterns (DAMPs) by stressed or dying cells. Hematopoietic and bone marrow-derived cells migrate to renew the denuded cellular barrier. Soluble growth factors, interleukins, chemokines, arachidonic acid products, and discharges from airway smooth muscle cells aid epithelial and tissue repair. Metalloproteases and extracellular matrix influence the epithelial-to-mesenchymal matrix. Lung macrophages contribute to the repair and influence airway hyperresponsiveness. Airway wall thickening, subepithelial fibrosis, mucus metaplasia, myofibroblast hyperplasia, muscle cells hyperplasia and hypertrophy, and epithelial hypertrophy are characteristic features of the airway remodeling (136-word count).

2 citations


Cites background from "Epithelial cell restoration and reg..."

  • ...Hematopoietic and bone marrow-derived cells migrate to renew the denuded cellular barrier [34-38]....

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  • ...Soluble growth factors, G-protein-coupled receptor agonists, and liberations from airway smooth muscle cells contribute to epithelial and tissue repair [34,38,41,42,46-50]....

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References
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Journal ArticleDOI
TL;DR: The acute respiratory distress syndrome (ARDS), a process of nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, carries a high morbidity, mortality, and financial cost.
Abstract: The acute respiratory distress syndrome (ARDS), a process of nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, carries a high morbidity, mortality (10 to 90%), and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged, and it may be different in Europe. Part of the reason for these uncertainties are the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those who wish to know the true incidence and outcome of this clinical syndrome are stymied. The American-European Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important in order to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS.

6,233 citations

Journal ArticleDOI
TL;DR: It is estimated that each year in the United States there are 190,600 cases of acute lung injury, which are associated with 74,500 deaths and 3.6 million hospital days, considerably higher than previous reports have suggested.
Abstract: BACKGROUND Acute lung injury is a critical illness syndrome consisting of acute hypoxemic respiratory failure with bilateral pulmonary infiltrates that are not attributed to left atrial hypertension. Despite recent advances in our understanding of the mechanism and treatment of acute lung injury, its incidence and outcomes in the United States have been unclear. METHODS We conducted a prospective, population-based, cohort study in 21 hospitals in and around King County, Washington, from April 1999 through July 2000, using a validated screening protocol to identify patients who met the consensus criteria for acute lung injury. RESULTS A total of 1113 King County residents undergoing mechanical ventilation met the criteria for acute lung injury and were 15 years of age or older. On the basis of this figure, the crude incidence of acute lung injury was 78.9 per 100,000 person-years and the age-adjusted incidence was 86.2 per 100,000 person-years. The in-hospital mortality rate was 38.5 percent. The incidence of acute lung injury increased with age from 16 per 100,000 person-years for those 15 through 19 years of age to 306 per 100,000 person-years for those 75 through 84 years of age. Mortality increased with age from 24 percent for patients 15 through 19 years of age to 60 percent for patients 85 years of age or older (P<0.001). We estimate that each year in the United States there are 190,600 cases of acute lung injury, which are associated with 74,500 deaths and 3.6 million hospital days. CONCLUSIONS Acute lung injury has a substantial impact on public health, with an incidence in the United States that is considerably higher than previous reports have suggested.

3,358 citations

Journal ArticleDOI
04 May 2001-Cell
TL;DR: It is shown that rare cells that home to bone marrow can LTR primary and secondary recipients, and this finding may contribute to clinical treatment of genetic disease or tissue repair.

2,773 citations

Journal ArticleDOI
17 Jun 2005-Cell
TL;DR: Although bronchiolar cells and alveolar cells are proposed to be the precursor cells of adenocarcinoma, this work points to bronchioalveolar stem cells as the putative cells of origin for this subtype of lung cancer.

2,087 citations

Journal ArticleDOI
TL;DR: Given the poor prognosis associated with idiopathic pulmonary fibrosis, patients should be referred to regional centers of expertise for enrollment in therapeutic clinical trials or for lung transplantation.
Abstract: Idiopathic pulmonary fibrosis is a rapidly progressive illness of unknown cause characterized by sequential acute lung injury with subsequent scarring and end-stage lung disease. Treatment at present remains largely supportive, with evidence that patients' satisfaction and survival may be improved by referral to centers specializing in the evaluation of interstitial lung diseases. Although no drug therapy has clearly been demonstrated to benefit patients with idiopathic pulmonary fibrosis, a number of novel investigational agents hold promise for future study. Given the poor prognosis associated with idiopathic pulmonary fibrosis, patients should be referred to regional centers of expertise for enrollment in therapeutic clinical trials or for lung transplantation.

905 citations

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