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Annual Review of Physiology Feb 2020People worldwide are living longer, and it is estimated that by 2050, the proportion of the world's population over 60 years of age will nearly double. Natural lung... (Review)
Review
People worldwide are living longer, and it is estimated that by 2050, the proportion of the world's population over 60 years of age will nearly double. Natural lung aging is associated with molecular and physiological changes that cause alterations in lung function, diminished pulmonary remodeling and regenerative capacity, and increased susceptibility to acute and chronic lung diseases. As the aging population rapidly grows, it is essential to examine how alterations in cellular function and cell-to-cell interactions of pulmonary resident cells and systemic immune cells contribute to a higher risk of increased susceptibility to infection and development of chronic diseases, such as chronic obstructive pulmonary disease and interstitial pulmonary fibrosis. This review provides an overview of physiological, structural, and cellular changes in the aging lung and immune system that facilitate the development and progression of disease.
Topics: Aged; Aging; Cellular Senescence; Humans; Lung; Lung Diseases; Middle Aged
PubMed: 31730381
DOI: 10.1146/annurev-physiol-021119-034610 -
Nature Reviews. Disease Primers Nov 2019In the absence of effective interventions to prevent preterm births, improved survival of infants who are born at the biological limits of viability has relied on... (Review)
Review
In the absence of effective interventions to prevent preterm births, improved survival of infants who are born at the biological limits of viability has relied on advances in perinatal care over the past 50 years. Except for extremely preterm infants with suboptimal perinatal care or major antenatal events that cause severe respiratory failure at birth, most extremely preterm infants now survive, but they often develop chronic lung dysfunction termed bronchopulmonary dysplasia (BPD; also known as chronic lung disease). Despite major efforts to minimize injurious but often life-saving postnatal interventions (such as oxygen, mechanical ventilation and corticosteroids), BPD remains the most frequent complication of extreme preterm birth. BPD is now recognized as the result of an aberrant reparative response to both antenatal injury and repetitive postnatal injury to the developing lungs. Consequently, lung development is markedly impaired, which leads to persistent airway and pulmonary vascular disease that can affect adult lung function. Greater insights into the pathobiology of BPD will provide a better understanding of disease mechanisms and lung repair and regeneration, which will enable the discovery of novel therapeutic targets. In parallel, clinical and translational studies that improve the classification of disease phenotypes and enable early identification of at-risk preterm infants should improve trial design and individualized care to enhance outcomes in preterm infants.
Topics: Adrenal Cortex Hormones; Bronchopulmonary Dysplasia; Humans; Infant, Newborn; Infant, Premature; Lung
PubMed: 31727986
DOI: 10.1038/s41572-019-0127-7 -
American Journal of Physiology. Cell... Oct 2020The ability to replace defective cells in an airway with cells that can engraft, integrate, and restore a functional epithelium could potentially cure a number of lung... (Review)
Review
The ability to replace defective cells in an airway with cells that can engraft, integrate, and restore a functional epithelium could potentially cure a number of lung diseases. Progress toward the development of strategies to regenerate the adult lung by either in vivo or ex vivo targeting of endogenous stem cells or pluripotent stem cell derivatives is limited by our fundamental lack of understanding of the mechanisms controlling human lung development, the precise identity and function of human lung stem and progenitor cell types, and the genetic and epigenetic control of human lung fate. In this review, we intend to discuss the known stem/progenitor cell populations, their relative differences between rodents and humans, their roles in chronic lung disease, and their therapeutic prospects. Additionally, we highlight the recent breakthroughs that have increased our understanding of these cell types. These advancements include novel lineage-traced animal models and single-cell RNA sequencing of human airway cells, which have provided critical information on the stem cell subtypes, transition states, identifying cell markers, and intricate pathways that commit a stem cell to differentiate or to maintain plasticity. As our capacity to model the human lung evolves, so will our understanding of lung regeneration and our ability to target endogenous stem cells as a therapeutic approach for lung disease.
Topics: Cell Differentiation; Epithelium; Humans; Lung; Lung Diseases; Pluripotent Stem Cells; Regeneration
PubMed: 32783658
DOI: 10.1152/ajpcell.00036.2020 -
Gastroenterology Jan 2021The composition of the intestinal microbiome affects health from the prenatal period throughout childhood, and many diseases have been associated with dysbiosis. The gut... (Review)
Review
The composition of the intestinal microbiome affects health from the prenatal period throughout childhood, and many diseases have been associated with dysbiosis. The gut microbiome is constantly changing, from birth throughout adulthood, and several variables affect its development and content. Features of the intestinal microbiota can affect development of the brain, immune system, and lungs, as well as body growth. We review the development of the gut microbiome, proponents of dysbiosis, and interactions of the microbiota with other organs. The gut microbiome should be thought of as an organ system that has important effects on childhood development. Dysbiosis has been associated with diseases in children and adults, including autism, attention deficit hyperactivity disorder, asthma, and allergies.
Topics: Adolescent; Body Weight; Central Nervous System; Child; Child Development; Child, Preschool; Dysbiosis; Environment; Female; Gastrointestinal Microbiome; Health; Health Status; Humans; Immune System; Infant; Infant, Newborn; Lung
PubMed: 33307032
DOI: 10.1053/j.gastro.2020.08.065 -
Development (Cambridge, England) Feb 2014The respiratory system, which consists of the lungs, trachea and associated vasculature, is essential for terrestrial life. In recent years, extensive progress has been... (Review)
Review
The respiratory system, which consists of the lungs, trachea and associated vasculature, is essential for terrestrial life. In recent years, extensive progress has been made in defining the temporal progression of lung development, and this has led to exciting discoveries, including the derivation of lung epithelium from pluripotent stem cells and the discovery of developmental pathways that are targets for new therapeutics. These discoveries have also provided new insights into the regenerative capacity of the respiratory system. This Review highlights recent advances in our understanding of lung development and regeneration, which will hopefully lead to better insights into both congenital and acquired lung diseases.
Topics: Animals; Humans; Lung; Models, Biological; Organogenesis; Regeneration
PubMed: 24449833
DOI: 10.1242/dev.098186 -
Physiology (Bethesda, Md.) May 2017The main function of the lung is to support gas exchange, and defects in lung development or diseases affecting the structure and function of the lung can have fatal... (Review)
Review
The main function of the lung is to support gas exchange, and defects in lung development or diseases affecting the structure and function of the lung can have fatal consequences. Most of what we currently understand about human lung development and disease has come from animal models. However, animal models are not always fully able to recapitulate human lung development and disease, highlighting an area where in vitro models of the human lung can compliment animal models to further understanding of critical developmental and pathological mechanisms. This review will discuss current advances in generating in vitro human lung models using primary human tissue, cell lines, and human pluripotent stem cell derived lung tissue, and will discuss crucial next steps in the field.
Topics: Animals; Cell Culture Techniques; Cell Line; Disease Models, Animal; Homeostasis; Humans; In Vitro Techniques; Lung; Lung Diseases; Models, Biological; Pluripotent Stem Cells; Regeneration
PubMed: 28404740
DOI: 10.1152/physiol.00041.2016 -
Annals of the American Thoracic Society Dec 2016The onset of chronic obstructive pulmonary disease (COPD) can arise either from failure to attain the normal spirometric plateau or from an accelerated decline in lung... (Review)
Review
The onset of chronic obstructive pulmonary disease (COPD) can arise either from failure to attain the normal spirometric plateau or from an accelerated decline in lung function. Despite reports from numerous big cohorts, no single adult life factor, including smoking, accounts for this accelerated decline. By contrast, five childhood risk factors (maternal and paternal asthma, maternal smoking, childhood asthma and respiratory infections) are strongly associated with an accelerated rate of lung function decline and COPD. Among adverse effects on lung development are transgenerational (grandmaternal smoking), antenatal (exposure to tobacco and pollution), and early childhood (exposure to tobacco and pollution including pesticides) factors. Antenatal adverse events can operate by causing structural changes in the developing lung, causing low birth weight and prematurity and altered immunological responses. Also important are mode of delivery, early microbiological exposures, and multiple early atopic sensitizations. Early bronchial hyperresponsiveness, before any evidence of airway inflammation, is associated with adverse respiratory outcomes. Overlapping cohort studies established that spirometry tracks from the preschool years to late middle age, and those with COPD in the sixth decade already had the worst spirometry at age 10 years. Alveolar development is now believed to continue throughout somatic growth and is adversely impacted by early tobacco smoke exposure. Genetic factors are also important, with genes important in lung development and early wheezing also being implicated in COPD. The inescapable conclusion is that the roots of COPD are in early life, and COPD is a disease of childhood adverse factors interacting with genetic factors.
Topics: Aging; Air Pollution; Asthma; Disease Progression; Environmental Exposure; Female; Humans; Lung; Microbiota; Pesticides; Pregnancy; Prenatal Exposure Delayed Effects; Pulmonary Disease, Chronic Obstructive; Tobacco Smoke Pollution
PubMed: 28005431
DOI: 10.1513/AnnalsATS.201602-112AW -
Biomaterials Jan 2017Organoids represent both a potentially powerful tool for the study cell-cell interactions within tissue-like environments, and a platform for tissue regenerative...
Organoids represent both a potentially powerful tool for the study cell-cell interactions within tissue-like environments, and a platform for tissue regenerative approaches. The development of lung tissue-like organoids from human adult-derived cells has not previously been reported. Here we combined human adult primary bronchial epithelial cells, lung fibroblasts, and lung microvascular endothelial cells in supportive 3D culture conditions to generate airway organoids. We demonstrate that randomly-seeded mixed cell populations undergo rapid condensation and self-organization into discrete epithelial and endothelial structures that are mechanically robust and stable during long term culture. After condensation airway organoids generate invasive multicellular tubular structures that recapitulate limited aspects of branching morphogenesis, and require actomyosin-mediated force generation and YAP/TAZ activation. Despite the proximal source of primary epithelium used in the airway organoids, discrete areas of both proximal and distal epithelial markers were observed over time in culture, demonstrating remarkable epithelial plasticity within the context of organoid cultures. Airway organoids also exhibited complex multicellular responses to a prototypical fibrogenic stimulus (TGF-β1) in culture, and limited capacity to undergo continued maturation and engraftment after ectopic implantation under the murine kidney capsule. These results demonstrate that the airway organoid system developed here represents a novel tool for the study of disease-relevant cell-cell interactions, and establishes this platform as a first step toward cell-based therapy for chronic lung diseases based on de novo engineering of implantable airway tissues.
Topics: Adult; Animals; Cell Differentiation; Cell Line; Cells, Cultured; Endothelial Cells; Epithelial Cells; Humans; Lung; Mesenchymal Stem Cells; Mice; Organ Culture Techniques; Organogenesis; Organoids; Regeneration; Tissue Engineering
PubMed: 27815996
DOI: 10.1016/j.biomaterials.2016.10.046 -
Nutrients Jul 2018Experimental evidence from animal models and epidemiology studies has demonstrated that nutrition affects lung development and may have a lifelong impact on respiratory... (Review)
Review
Experimental evidence from animal models and epidemiology studies has demonstrated that nutrition affects lung development and may have a lifelong impact on respiratory health. Chronic restriction of nutrients and/or oxygen during pregnancy causes structural changes in the airways and parenchyma that may result in abnormal lung function, which is tracked throughout life. Inadequate nutritional management in very premature infants hampers lung growth and may be a contributing factor in the pathogenesis of bronchopulmonary dysplasia. Recent evidence seems to indicate that infant and childhood malnutrition does not determine lung function impairment even in the presence of reduced lung size due to delayed body growth. This review will focus on the effects of malnutrition occurring at critical time periods such as pregnancy, early life, and childhood, on lung growth and long-term lung function.
Topics: Adult; Animals; Bronchopulmonary Dysplasia; Child; Child Nutritional Physiological Phenomena; Diet, Healthy; Evidence-Based Medicine; Female; Fetal Growth Retardation; Health Status; Humans; Infant, Newborn; Lung; Malnutrition; Maternal Nutritional Physiological Phenomena; Nutritional Status; Pregnancy; Pregnancy Complications; Respiratory Tract Diseases
PubMed: 30021997
DOI: 10.3390/nu10070919 -
Current Topics in Developmental Biology 2010Developmental lung biology is a field that has the potential for significant human impact: lung disease at the extremes of age continues to cause major morbidity and... (Review)
Review
Developmental lung biology is a field that has the potential for significant human impact: lung disease at the extremes of age continues to cause major morbidity and mortality worldwide. Understanding how the lung develops holds the promise that investigators can use this knowledge to aid lung repair and regeneration. In the decade since the "molecular embryology" of the lung was first comprehensively reviewed, new challenges have emerged-and it is on these that we focus the current review. Firstly, there is a critical need to understand the progenitor cell biology of the lung in order to exploit the potential of stem cells for the treatment of lung disease. Secondly, the current familiar descriptions of lung morphogenesis governed by growth and transcription factors need to be elaborated upon with the reinclusion and reconsideration of other factors, such as mechanics, in lung growth. Thirdly, efforts to parse the finer detail of lung bud signaling may need to be combined with broader consideration of overarching mechanisms that may be therapeutically easier to target: in this arena, we advance the proposal that looking at the lung in general (and branching in particular) in terms of clocks may yield unexpected benefits.
Topics: Animals; Biomechanical Phenomena; Cell Proliferation; Epithelial Cells; Homeodomain Proteins; Humans; Intercellular Signaling Peptides and Proteins; Lung; MicroRNAs; Organogenesis; Signal Transduction; Stem Cells; Transcription Factors
PubMed: 20691848
DOI: 10.1016/S0070-2153(10)90003-3