1,721,097 research outputs found
Stem/Progenitor Cell Populations Resident in the Lung and the Role of Stromal Support in Their Maintenance and Differentiation
Full text linkLungs are vital organs for respiration, being enabled by their complex three-dimensional organization [1]. Airway tubes bifurcate into millions of highly vascularized alveolar sacs, the alveoli, which are responsible for gas exchange. The gas exchange surface of the lungs makes up one of the largest surface areas of the human body. The alveoli receive air from the conducting airways, starting in the trachea, bifurcating into the bronchi and bronchioles, and ending in the terminal bronchioles, which divide into the alveolar ducts from which the alveoli arise. The aim of this chapter is to provide an overview of the progenitors in adult lung tissue and the regulation of their maintenance and differentiation by the microenvironment during lung developmental as well as repair processes, when developmental pathways are often reactivated. As most work has been done in mouse studies, the current knowledge from animal studies will be summarized and translated to what is known from human lungs. In order to understand the regenerative processes in the lung, we will first provide insight into the complex three-dimensional organization and composition of the lung, its function, and the processes involved in lung development.</p
Challenges and Opportunities for the Future of Stem Cell Therapy for Lung Diseases
Full text linkIn this era of striving for personalized medicine approaches for complex diseases, preclinical studies have excited the field through their demonstration of the promise of stem cell therapy for the treatment of various lung diseases; with the most beneficial effects of stem cell-based strategies in preclinical settings originating from their antimicrobial, anti-inflammatory, and immunomodulatory properties. Although many lung disorders involve an inflammatory component, effective stem cell therapy in patients has not been realized yet for the majority of lung diseases and there are still multiple hurdles to be overcome. While beneficial effects have been realized in clinical studies of CF, results from clinical studies in other lung diseases have been disappointing to date. We discuss the questions that should be addressed before considering administration of stem cells or their derivatives in a phase I studies. We should prevent stem cell tourism, where cell-based therapies are being marketed to extremely vulnerable patient populations and their caregivers. Unproven and often unsafe stem cell treatment practices can mislead patients into participating in often very expensive, unregulated, unethical, and unsafe treatments, which are not covered by insurance. Here, the education of patients, caregivers and of pulmonologists who are not familiar with the stem cell field will be of great value.</p
Chronic lung pathologies that require repair and regeneration.
Full text linkChronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, are a major cause of mortality worldwide. With the increasing incidence with ageing, the full impact of these diseases is yet to be realised. For most chronic lung diseases there are limited treatments options, with the existing approaches mainly addressing symptom relief. Little progress has been made, in recent years, in the development of new therapeutic strategies for managing these burdensome pathologies. There is an urgent need to increase our understanding of the mechanisms underlying these diseases. Endogenous progenitor cells (stem cells) have been recognised in many organs, including the lungs where they are suggested to maintain a population of cells that are able to facilitate the endogenous repair processes. Emerging knowledge of how these repair processes are disrupted in chronic lung diseases and the potential to capitalise upon the regenerative capacity of stem cell populations raise the hopes of the field worldwide for innovative treatment approaches for these devastating diseases in the future. This chapter outlines the series of diseases that may benefit from these emerging new therapeutic outlooks
Chronic lung pathologies that require repair and regeneration.
No full textChronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, are a major cause of mortality worldwide. With the increasing incidence with ageing, the full impact of these diseases is yet to be realised. For most chronic lung diseases there are limited treatments options, with the existing approaches mainly addressing symptom relief. Little progress has been made, in recent years, in the development of new therapeutic strategies for managing these burdensome pathologies. There is an urgent need to increase our understanding of the mechanisms underlying these diseases. Endogenous progenitor cells (stem cells) have been recognised in many organs, including the lungs where they are suggested to maintain a population of cells that are able to facilitate the endogenous repair processes. Emerging knowledge of how these repair processes are disrupted in chronic lung diseases and the potential to capitalise upon the regenerative capacity of stem cell populations raise the hopes of the field worldwide for innovative treatment approaches for these devastating diseases in the future. This chapter outlines the series of diseases that may benefit from these emerging new therapeutic outlooks
Preclinical evidence for the role of stem/stromal cells in COPD
No full textChronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide and there are currently limited treatment options for these patients. The disease is characterized by a reduction in airflow due to chronic bronchitis, as well as airspace enlargement in the distal lung, resulting in a loss of surface area available for gas exchange. At end-stage disease, oxygen therapy and lung transplantation remain the only potential options. The disease is heterogeneous and both inflammatory cells as well as structural cells are thought to play a role in disease onset and progression. Pharmaceutical approaches are ineffective at reversing disease pathology and currently aim only to provide symptomatic relief. A recent area of investigation focuses on exogenous cell therapy, including stem cell administration, and its potential for directing lung regeneration. Cell therapies from a variety of sources, as well as cell-derived products such as extracellular vesicles, have recently shown efficacy in animal models of COPD, but early clinical trials have not yet shown efficacy. In this chapter, we discuss the different animal models of COPD as well as the studies which have been conducted to date with cell therapies. We conclude the chapter with a discussion regarding the limitations of current animal models and discuss potential areas for future study
Chronic lung pathologies that require repair and regeneration.
Full text linkChronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, are a major cause of mortality worldwide. With the increasing incidence with ageing, the full impact of these diseases is yet to be realised. For most chronic lung diseases there are limited treatments options, with the existing approaches mainly addressing symptom relief. Little progress has been made, in recent years, in the development of new therapeutic strategies for managing these burdensome pathologies. There is an urgent need to increase our understanding of the mechanisms underlying these diseases. Endogenous progenitor cells (stem cells) have been recognised in many organs, including the lungs where they are suggested to maintain a population of cells that are able to facilitate the endogenous repair processes. Emerging knowledge of how these repair processes are disrupted in chronic lung diseases and the potential to capitalise upon the regenerative capacity of stem cell populations raise the hopes of the field worldwide for innovative treatment approaches for these devastating diseases in the future. This chapter outlines the series of diseases that may benefit from these emerging new therapeutic outlooks
Chronic lung pathologies that require repair and regeneration.
Full text linkChronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, are a major cause of mortality worldwide. With the increasing incidence with ageing, the full impact of these diseases is yet to be realised. For most chronic lung diseases there are limited treatments options, with the existing approaches mainly addressing symptom relief. Little progress has been made, in recent years, in the development of new therapeutic strategies for managing these burdensome pathologies. There is an urgent need to increase our understanding of the mechanisms underlying these diseases. Endogenous progenitor cells (stem cells) have been recognised in many organs, including the lungs where they are suggested to maintain a population of cells that are able to facilitate the endogenous repair processes. Emerging knowledge of how these repair processes are disrupted in chronic lung diseases and the potential to capitalise upon the regenerative capacity of stem cell populations raise the hopes of the field worldwide for innovative treatment approaches for these devastating diseases in the future. This chapter outlines the series of diseases that may benefit from these emerging new therapeutic outlooks
Compartmentalized signaling in the lung: A-kinase anchoring proteins as novel drug targets for chronic obstructive pulmonary disease
Full text linkWilfred Poppinga aimed to unravel the role of A-kinase anchoring proteins (AKAPs) in the lung in relation to chronic obstructive pulmonary disease (COPD). COPD is an inflammatory disease particularly caused by cigarette smoking, with patients suffering from chronic and progressive airway obstruction that is treated with bronchodilators, including β2-agonists. AKAPs bind protein kinase A (PKA), which may be important for mediating β2-agonist-induced responses in the airways. Poppinga and colleagues focused on the role of AKAPs in the regulation of bronchodilatory actions of β2-agonists as well as pulmonary inflammation in the context of COPD. It was found that human airway smooth muscle cells, which play a role both in bronchoconstriction and inflammation, express several AKAPs, including AKAP5 and AKAP12, known to bind the β2-adrenoceptor. Importantly, the amount of AKAP5 and AKAP12 was lower in lungs from COPD patients, which may be related to smoking as cigarette smoke extract reduced their expression in airway smooth muscle cells. Disruption of AKAP-PKA interactions with st-Ht31 in airway smooth muscle cells increased cigarette smoke extract-induced release of the pro-inflammatory interleukin-8, which attracts neutrophilic inflammatory cells. In line with this, cigarette smoke induced a stronger neutrophilic inflammation in mice that lack AKAP5. Mice lacking AKAP12 already had increased infiltration of inflammatory cells in the lung at baseline. Mice lacking AKAP12 also showed reduced β2-agonist-induced airway smooth muscle relaxation. In line, different variants (single nucleotide polymorphisms) of the human AKAP12 gene were found, that affect the amino acid sequence but not the gene expression of AKAP12 and that were associated with a varying β2-agonist-induced bronchodilation. The reduction in AKAP5 and AKAP12 in COPD could therefore contribute to pulmonary inflammation, particularly neutrophilia, and may limit β2-agonist-induced bronchodilation. Therefore, restoring AKAP5 and/or AKAP12 expression could decrease COPD progression and enhance pharmacological treatment of this disease
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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