CORD-19-Sentences  

CORD-19:0376103fd7863b10e41a0f59fe226be9765f34c7 JSONTXT 9 Projects

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Id Subject Object Predicate Lexical cue
TextSentencer_T1 0-101 Sentence denotes Cell-Based Strategies to Reconstitute Lung Function in Infants with Severe Bronchopulmonary Dysplasia
TextSentencer_T1 0-101 Sentence denotes Cell-Based Strategies to Reconstitute Lung Function in Infants with Severe Bronchopulmonary Dysplasia
TextSentencer_T2 103-111 Sentence denotes Abstract
TextSentencer_T2 103-111 Sentence denotes Abstract
TextSentencer_T3 114-262 Sentence denotes Extreme prematurity is one of the major risk factors for the development of chronic lung disease of prematurity or bronchopulmonary dysplasia (BPD).
TextSentencer_T3 114-262 Sentence denotes Extreme prematurity is one of the major risk factors for the development of chronic lung disease of prematurity or bronchopulmonary dysplasia (BPD).
TextSentencer_T4 263-498 Sentence denotes 1 Preterm infants born between 24 and 28 weeks of gestation (ie, extremely preterm) have an immature pulmonary surfactant system, immature airway and vascular architecture, and an underdeveloped surface area for gas exchange (Fig. 1) .
TextSentencer_T4 263-498 Sentence denotes 1 Preterm infants born between 24 and 28 weeks of gestation (ie, extremely preterm) have an immature pulmonary surfactant system, immature airway and vascular architecture, and an underdeveloped surface area for gas exchange (Fig. 1) .
TextSentencer_T5 499-638 Sentence denotes 2 Many very preterm infants require prolonged respiratory support to ensure survival, which further increases their risk of developing BPD.
TextSentencer_T5 499-638 Sentence denotes 2 Many very preterm infants require prolonged respiratory support to ensure survival, which further increases their risk of developing BPD.
TextSentencer_T6 639-746 Sentence denotes Recent evidence suggests that BPD may have long-term respiratory complications that reach beyond childhood.
TextSentencer_T6 639-746 Sentence denotes Recent evidence suggests that BPD may have long-term respiratory complications that reach beyond childhood.
TextSentencer_T7 747-1021 Sentence denotes Numerous follow-up studies indicate that children and young adults who were born very preterm are at an increased risk of respiratory symptoms, poor lung function, and lower exercise capacity [3] [4] [5] [6] [7] this is especially apparent in infants who have developed BPD.
TextSentencer_T7 747-1021 Sentence denotes Numerous follow-up studies indicate that children and young adults who were born very preterm are at an increased risk of respiratory symptoms, poor lung function, and lower exercise capacity [3] [4] [5] [6] [7] this is especially apparent in infants who have developed BPD.
TextSentencer_T8 1022-1227 Sentence denotes More alarmingly, isolated case studies are surfacing of irreversible arrested alveolar development at adult age in former premature infants with BPD, 8, 9 mirroring results from experimental models of BPD.
TextSentencer_T8 1022-1227 Sentence denotes More alarmingly, isolated case studies are surfacing of irreversible arrested alveolar development at adult age in former premature infants with BPD, 8, 9 mirroring results from experimental models of BPD.
TextSentencer_T9 1228-1519 Sentence denotes 10 Progress toward decreasing the incidence/severity of BPD over the next few years using currently available techniques and strategies is likely (ie, optimization of antenatal management combined with surfactant and early noninvasive ventilatory support targeting lower oxygen saturations).
TextSentencer_T9 1228-1519 Sentence denotes 10 Progress toward decreasing the incidence/severity of BPD over the next few years using currently available techniques and strategies is likely (ie, optimization of antenatal management combined with surfactant and early noninvasive ventilatory support targeting lower oxygen saturations).
TextSentencer_T10 1520-1751 Sentence denotes 11 However, further understanding of the mechanisms involved in lung development, injury, and repair are necessary to advance toward preventing lung injury and/or promoting lung development/regeneration in prematurely born infants.
TextSentencer_T10 1520-1751 Sentence denotes 11 However, further understanding of the mechanisms involved in lung development, injury, and repair are necessary to advance toward preventing lung injury and/or promoting lung development/regeneration in prematurely born infants.
TextSentencer_T11 1752-1913 Sentence denotes Exciting discoveries in stem cell biology in recent years may offer new insight into the pathogenesis of BPD and, more importantly, open new therapeutic avenues.
TextSentencer_T11 1752-1913 Sentence denotes Exciting discoveries in stem cell biology in recent years may offer new insight into the pathogenesis of BPD and, more importantly, open new therapeutic avenues.
TextSentencer_T12 1914-2058 Sentence denotes Stem cells are primitive cells capable of extensive self-renewal with the potential to give rise to multiple differentiated cellular phenotypes.
TextSentencer_T12 1914-2058 Sentence denotes Stem cells are primitive cells capable of extensive self-renewal with the potential to give rise to multiple differentiated cellular phenotypes.
TextSentencer_T13 2059-2233 Sentence denotes 12 These cells are not only critical for organogenesis and growth during the early stages of development but also contribute to organ repair and regeneration throughout life.
TextSentencer_T13 2059-2233 Sentence denotes 12 These cells are not only critical for organogenesis and growth during the early stages of development but also contribute to organ repair and regeneration throughout life.
TextSentencer_T14 2234-2346 Sentence denotes The concept of developmental potency refers to the range of possible fates open to cells during differentiation.
TextSentencer_T14 2234-2346 Sentence denotes The concept of developmental potency refers to the range of possible fates open to cells during differentiation.
TextSentencer_T15 2347-2469 Sentence denotes Stem cells exhibit varying differentiation potencies, and are typically categorized into embryonic and somatic stem cells.
TextSentencer_T15 2347-2469 Sentence denotes Stem cells exhibit varying differentiation potencies, and are typically categorized into embryonic and somatic stem cells.
TextSentencer_T16 2470-2771 Sentence denotes Embryonic stem cells (ESCs) are derived from the early blastocyst and represent the most potent of stem cells owing to their pluripotency (ie, ability to differentiate into cell types derived from all 3 germinal lineages: endoderm, mesoderm, or ectoderm) and their ability for indefinite self-renewal.
TextSentencer_T16 2470-2771 Sentence denotes Embryonic stem cells (ESCs) are derived from the early blastocyst and represent the most potent of stem cells owing to their pluripotency (ie, ability to differentiate into cell types derived from all 3 germinal lineages: endoderm, mesoderm, or ectoderm) and their ability for indefinite self-renewal.
TextSentencer_T17 2772-3047 Sentence denotes By contrast, somatic stem cells (also termed adult stem cells [ASCs] ) are cells that have assumed increasing degrees of fate restriction and are either multipotent (ie, can differentiate into a limited range of cell types) or unipotent (ie, can generate only one cell type).
TextSentencer_T17 2772-3047 Sentence denotes By contrast, somatic stem cells (also termed adult stem cells [ASCs] ) are cells that have assumed increasing degrees of fate restriction and are either multipotent (ie, can differentiate into a limited range of cell types) or unipotent (ie, can generate only one cell type).
TextSentencer_T18 3048-3285 Sentence denotes 13 Residual pools of such multipotent or unipotent stem cells are hypothesized to reside in almost all adult organs, and have the ability to contribute to tissue repair and regeneration via repopulation during growth, injury, or disease.
TextSentencer_T18 3048-3285 Sentence denotes 13 Residual pools of such multipotent or unipotent stem cells are hypothesized to reside in almost all adult organs, and have the ability to contribute to tissue repair and regeneration via repopulation during growth, injury, or disease.
TextSentencer_T19 3286-3445 Sentence denotes While stem cells are essential for growth and development, residual pools of ASCs are considered important for tissue repair and maintenance through adulthood.
TextSentencer_T19 3286-3445 Sentence denotes While stem cells are essential for growth and development, residual pools of ASCs are considered important for tissue repair and maintenance through adulthood.
TextSentencer_T20 3446-3658 Sentence denotes Highly proliferative tissues, such as the intestinal epithelium or the hematopoietic compartment of the bone marrow, depend on a pool of ASCs that are organized in a "classical hierarchy" to maintain homeostasis.
TextSentencer_T20 3446-3658 Sentence denotes Highly proliferative tissues, such as the intestinal epithelium or the hematopoietic compartment of the bone marrow, depend on a pool of ASCs that are organized in a "classical hierarchy" to maintain homeostasis.
TextSentencer_T21 3659-3825 Sentence denotes 14 By contrast, anatomically complex tissues that turn over more slowly (ie, brain, heart, lung, and kidney) do not appear to support a classical stem cell hierarchy.
TextSentencer_T21 3659-3825 Sentence denotes 14 By contrast, anatomically complex tissues that turn over more slowly (ie, brain, heart, lung, and kidney) do not appear to support a classical stem cell hierarchy.
TextSentencer_T22 3826-4027 Sentence denotes Such tissues are thought to be maintained by stem/progenitor cell populations that are organized in a nonclassical hierarchy and are recruited in a facultative manner for regeneration following injury.
TextSentencer_T22 3826-4027 Sentence denotes Such tissues are thought to be maintained by stem/progenitor cell populations that are organized in a nonclassical hierarchy and are recruited in a facultative manner for regeneration following injury.
TextSentencer_T23 4028-4224 Sentence denotes In the lung, several local epithelial cell types function both as differentiated functional cells and as transit-amplifying progenitors that proliferate in response to airway or alveolar injuries.
TextSentencer_T23 4028-4224 Sentence denotes In the lung, several local epithelial cell types function both as differentiated functional cells and as transit-amplifying progenitors that proliferate in response to airway or alveolar injuries.
TextSentencer_T24 4225-4629 Sentence denotes 15 Recent research suggests that the adult lung harbors rare populations of multipotent epithelial stem cells that are regulated by specific microenvironmental cellular niches, and are putatively recruited to repopulate the damaged epithelium. [16] [17] [18] [19] With new insights into stem cell biology, other types of resident lung stem/progenitor cells have also been described over the past 5 years.
TextSentencer_T24 4225-4629 Sentence denotes 15 Recent research suggests that the adult lung harbors rare populations of multipotent epithelial stem cells that are regulated by specific microenvironmental cellular niches, and are putatively recruited to repopulate the damaged epithelium. [16] [17] [18] [19] With new insights into stem cell biology, other types of resident lung stem/progenitor cells have also been described over the past 5 years.
TextSentencer_T25 4630-4725 Sentence denotes Lungs are complex organs constituted by more than 40 cell types derived from all 3 germ layers.
TextSentencer_T25 4630-4725 Sentence denotes Lungs are complex organs constituted by more than 40 cell types derived from all 3 germ layers.
TextSentencer_T26 4726-4959 Sentence denotes 20 Normal lung morphogenesis involves spatiotemporally coordinated interactions between the stem/progenitor cells of different cellular compartments, which are later recapitulated during lung regeneration and repair following injury.
TextSentencer_T26 4726-4959 Sentence denotes 20 Normal lung morphogenesis involves spatiotemporally coordinated interactions between the stem/progenitor cells of different cellular compartments, which are later recapitulated during lung regeneration and repair following injury.
TextSentencer_T27 4960-5135 Sentence denotes 21 At present, the localization and properties of lung stem/progenitor cell niches and the type of cells within each niche are of major interest, yet also present controversy.
TextSentencer_T27 4960-5135 Sentence denotes 21 At present, the localization and properties of lung stem/progenitor cell niches and the type of cells within each niche are of major interest, yet also present controversy.
TextSentencer_T28 5136-5301 Sentence denotes Complexity of the lung architecture combined with an extensive diversity of cell types and niches has hindered the identification of true lung stem/progenitor cells.
TextSentencer_T28 5136-5301 Sentence denotes Complexity of the lung architecture combined with an extensive diversity of cell types and niches has hindered the identification of true lung stem/progenitor cells.
TextSentencer_T29 5302-5589 Sentence denotes Because of the exceptionally low rate of epithelial cell turnover in the steady-state adult lung, the use of injury models has become necessary in unveiling the identity, fate, and specificity of resident lung stem/progenitor cells that contribute to homeostatic maintenance in the lung.
TextSentencer_T29 5302-5589 Sentence denotes Because of the exceptionally low rate of epithelial cell turnover in the steady-state adult lung, the use of injury models has become necessary in unveiling the identity, fate, and specificity of resident lung stem/progenitor cells that contribute to homeostatic maintenance in the lung.
TextSentencer_T30 5590-5762 Sentence denotes 22 In doing so, it has been observed that relatively differentiated airway and alveolar epithelial cell types are capable of proliferating in response to epithelial injury.
TextSentencer_T30 5590-5762 Sentence denotes 22 In doing so, it has been observed that relatively differentiated airway and alveolar epithelial cell types are capable of proliferating in response to epithelial injury.
TextSentencer_T31 5763-5961 Sentence denotes 15 This observation has drawn the focus of lung stem/progenitor cell research into identifying and defining those epithelial cell subpopulations that appear to contribute to postinjury regeneration.
TextSentencer_T31 5763-5961 Sentence denotes 15 This observation has drawn the focus of lung stem/progenitor cell research into identifying and defining those epithelial cell subpopulations that appear to contribute to postinjury regeneration.
TextSentencer_T32 5962-6360 Sentence denotes 15 Indeed, putative populations of such endogenous progenitor cells within the adult lung have been located in the basal layer of the Stem Cells and Bronchopulmonary Dysplasia proximal conducting airways (trachea and major bronchi) and more distally (bronchioles and alveolar ducts) within or near neuroendocrine bodies (NEBs), in the bronchoalveolar duct junction (BADJ), and the alveolar surface.
TextSentencer_T32 5962-6360 Sentence denotes 15 Indeed, putative populations of such endogenous progenitor cells within the adult lung have been located in the basal layer of the Stem Cells and Bronchopulmonary Dysplasia proximal conducting airways (trachea and major bronchi) and more distally (bronchioles and alveolar ducts) within or near neuroendocrine bodies (NEBs), in the bronchoalveolar duct junction (BADJ), and the alveolar surface.
TextSentencer_T33 6361-6473 Sentence denotes 23 A representative list of putative endogenous lung epithelial stem/progenitor cells is summarized in Table 1 .
TextSentencer_T33 6361-6473 Sentence denotes 23 A representative list of putative endogenous lung epithelial stem/progenitor cells is summarized in Table 1 .
TextSentencer_T34 6474-6632 Sentence denotes While stem/progenitor cells in the proximal airways have been explored more extensively, the study of distal stem/progenitor cells remains more controversial.
TextSentencer_T34 6474-6632 Sentence denotes While stem/progenitor cells in the proximal airways have been explored more extensively, the study of distal stem/progenitor cells remains more controversial.
TextSentencer_T35 6633-6764 Sentence denotes Airway submucosal glands (SMGs) and SMG ducts are major secretory structures situated below the epithelium of the proximal trachea.
TextSentencer_T35 6633-6764 Sentence denotes Airway submucosal glands (SMGs) and SMG ducts are major secretory structures situated below the epithelium of the proximal trachea.
TextSentencer_T36 6765-6900 Sentence denotes 24 Studies have indicated that SMGs may serve as a protective niche for adult epithelial stem/progenitor cells of the proximal airways.
TextSentencer_T36 6765-6900 Sentence denotes 24 Studies have indicated that SMGs may serve as a protective niche for adult epithelial stem/progenitor cells of the proximal airways.
TextSentencer_T37 6901-7226 Sentence denotes 25, 26 Using a model of epithelial damage induced by intratracheal detergent or SO 2 inhalation, Borthwick and colleagues 25 identified a population of 5-bromo-2 0 -deoxyuridine label-retaining cells that were localized to the gland ducts of the upper trachea and were able to reconstitute a surface-like tracheal epithelium.
TextSentencer_T37 6901-7226 Sentence denotes 25, 26 Using a model of epithelial damage induced by intratracheal detergent or SO 2 inhalation, Borthwick and colleagues 25 identified a population of 5-bromo-2 0 -deoxyuridine label-retaining cells that were localized to the gland ducts of the upper trachea and were able to reconstitute a surface-like tracheal epithelium.
TextSentencer_T38 7227-7450 Sentence denotes In support of these findings, SMG duct cells (K5 1 , K14 1 ) survive severe hypoxic-ischemic injury and contain stem/progenitor cell populations for regenerating the pseudostratified surface epithelium, SMGs, and SMG ducts.
TextSentencer_T38 7227-7450 Sentence denotes In support of these findings, SMG duct cells (K5 1 , K14 1 ) survive severe hypoxic-ischemic injury and contain stem/progenitor cell populations for regenerating the pseudostratified surface epithelium, SMGs, and SMG ducts.
TextSentencer_T39 7451-7739 Sentence denotes 26 An additional niche of stem/progenitor cells in the proximal airway is the K14expressing tracheobronchial basal cells, which have been shown to repopulate the denuded airway epithelium, including columnar secretory and ciliated cells, following naphthalene-induced epithelial ablation.
TextSentencer_T39 7451-7739 Sentence denotes 26 An additional niche of stem/progenitor cells in the proximal airway is the K14expressing tracheobronchial basal cells, which have been shown to repopulate the denuded airway epithelium, including columnar secretory and ciliated cells, following naphthalene-induced epithelial ablation.
TextSentencer_T40 7740-7867 Sentence denotes 27 This finding indicates that the K14expressing basal cells are implicated as a stem/progenitor cell for this airway location.
TextSentencer_T40 7740-7867 Sentence denotes 27 This finding indicates that the K14expressing basal cells are implicated as a stem/progenitor cell for this airway location.
TextSentencer_T41 7868-7959 Sentence denotes The potential contribution of these cells to the repair of the distal lung remains unknown.
TextSentencer_T41 7868-7959 Sentence denotes The potential contribution of these cells to the repair of the distal lung remains unknown.
TextSentencer_T42 7960-8145 Sentence denotes With transition from the proximal to distal airways, it can be seen that the notion of multiple niches supporting different populations and their progenitors within the lung is evident.
TextSentencer_T42 7960-8145 Sentence denotes With transition from the proximal to distal airways, it can be seen that the notion of multiple niches supporting different populations and their progenitors within the lung is evident.
TextSentencer_T43 8146-8315 Sentence denotes This idea is supported by studies using naphthalene to deplete the airways of Clara cells, revealing a subset of Clara cells that are CCSP 1 , yet naphthalene resistant.
TextSentencer_T43 8146-8315 Sentence denotes This idea is supported by studies using naphthalene to deplete the airways of Clara cells, revealing a subset of Clara cells that are CCSP 1 , yet naphthalene resistant.
TextSentencer_T44 8316-8555 Sentence denotes These cells, termed variant Clara (Clara V ) cells, exhibit stem cell characteristics, including ability to efflux Hoechst dye and Sca-1 expression, and have been located either within NEBs or at the bronchoalveolar duct junctions (BADJs).
TextSentencer_T44 8316-8555 Sentence denotes These cells, termed variant Clara (Clara V ) cells, exhibit stem cell characteristics, including ability to efflux Hoechst dye and Sca-1 expression, and have been located either within NEBs or at the bronchoalveolar duct junctions (BADJs).
TextSentencer_T45 8556-8729 Sentence denotes 28, 29 More recently, Volckaert and colleagues 30 also proposed that parabronchial smooth muscle cells (PSMCs) constitute a stem/progenitor cell niche for the Clara V cells.
TextSentencer_T45 8556-8729 Sentence denotes 28, 29 More recently, Volckaert and colleagues 30 also proposed that parabronchial smooth muscle cells (PSMCs) constitute a stem/progenitor cell niche for the Clara V cells.
TextSentencer_T46 8730-8916 Sentence denotes Activation of the Clara V cell for epithelial repair following naphthalene injury was shown to be dependent on the paracrine signaling of fibroblast growth factor 10 from the PSMC niche.
TextSentencer_T46 8730-8916 Sentence denotes Activation of the Clara V cell for epithelial repair following naphthalene injury was shown to be dependent on the paracrine signaling of fibroblast growth factor 10 from the PSMC niche.
TextSentencer_T47 8917-9086 Sentence denotes 30 Recently, multipotent stem cells in the distal lung capable of differentiating into epithelial cells specific to the bronchioles and the alveoli have been identified.
TextSentencer_T47 8917-9086 Sentence denotes 30 Recently, multipotent stem cells in the distal lung capable of differentiating into epithelial cells specific to the bronchioles and the alveoli have been identified.
TextSentencer_T48 9087-9331 Sentence denotes Kim and colleagues 17 demonstrated the existence of dual-lineage bronchoalveolar stem cells (BASCs) at the BADJ that express both bronchiolar (CCSP 1 ) and alveolar (SP-C 1 ) markers, which proliferate in response to airway and alveolar injury.
TextSentencer_T48 9087-9331 Sentence denotes Kim and colleagues 17 demonstrated the existence of dual-lineage bronchoalveolar stem cells (BASCs) at the BADJ that express both bronchiolar (CCSP 1 ) and alveolar (SP-C 1 ) markers, which proliferate in response to airway and alveolar injury.
TextSentencer_T49 9332-9491 Sentence denotes However, based on the techniques used, there has been some ambiguity regarding the lineage potential 23, 31 and contribution of these cells to alveolar repair.
TextSentencer_T49 9332-9491 Sentence denotes However, based on the techniques used, there has been some ambiguity regarding the lineage potential 23, 31 and contribution of these cells to alveolar repair.
TextSentencer_T50 9492-9775 Sentence denotes 32 McQualter and colleagues 18 used a multiparameter cell separation strategy and an organotypic in vitro clonogenic assay to detect and characterize a rare population of multipotent adult lung epithelial stem cells that give rise to airway and alveolar epithelial lineages in vitro.
TextSentencer_T50 9492-9775 Sentence denotes 32 McQualter and colleagues 18 used a multiparameter cell separation strategy and an organotypic in vitro clonogenic assay to detect and characterize a rare population of multipotent adult lung epithelial stem cells that give rise to airway and alveolar epithelial lineages in vitro.
TextSentencer_T51 9776-10405 Sentence denotes More recently, p63-expressing cells in the bronchiolar epithelium have been Abbreviations: BADJ, bronchoalveolar duct junction; BASC, bronchoalveolar stem cell; BrdU, 5-bromo-2 0 -deoxyuridine; CCSP, Clara cell secretory protein; Clara V , variant Clara; EpCAMhi, epithelial cell adhesion molecule Fgf10, fibroblast growth factor 10; NEBs, neuroendocrine bodies; Oct-4, octamer-binding transcription factor 4; PSMC, parabronchial smooth muscle cell; Sca-1, stem cell antigen 1; SMG, submucosal gland; SP-C, surfactant protein C; SSEA-1, stage-specific embryonic antigen-1; SARS-CoV, severe acute respiratory syndrome coronavirus.
TextSentencer_T51 9776-10405 Sentence denotes More recently, p63-expressing cells in the bronchiolar epithelium have been Abbreviations: BADJ, bronchoalveolar duct junction; BASC, bronchoalveolar stem cell; BrdU, 5-bromo-2 0 -deoxyuridine; CCSP, Clara cell secretory protein; Clara V , variant Clara; EpCAMhi, epithelial cell adhesion molecule Fgf10, fibroblast growth factor 10; NEBs, neuroendocrine bodies; Oct-4, octamer-binding transcription factor 4; PSMC, parabronchial smooth muscle cell; Sca-1, stem cell antigen 1; SMG, submucosal gland; SP-C, surfactant protein C; SSEA-1, stage-specific embryonic antigen-1; SARS-CoV, severe acute respiratory syndrome coronavirus.
TextSentencer_T52 10406-10544 Sentence denotes shown to undergo rapid proliferation after H1N1 influenza virus infection and to radiate to interbronchiolar regions of alveolar ablation.
TextSentencer_T52 10406-10544 Sentence denotes shown to undergo rapid proliferation after H1N1 influenza virus infection and to radiate to interbronchiolar regions of alveolar ablation.
TextSentencer_T53 10545-10637 Sentence denotes These cells assemble into Krt5 1 pods and initiate expression of markers typical of alveoli.
TextSentencer_T53 10545-10637 Sentence denotes These cells assemble into Krt5 1 pods and initiate expression of markers typical of alveoli.
TextSentencer_T54 10638-10769 Sentence denotes Gene-expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar-capillary network.
TextSentencer_T54 10638-10769 Sentence denotes Gene-expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar-capillary network.
TextSentencer_T55 10770-10930 Sentence denotes 33 The presence of such putative endogenous alveolar stem cell populations provides fresh hope of target-directed, regenerative therapies for alveolar diseases.
TextSentencer_T55 10770-10930 Sentence denotes 33 The presence of such putative endogenous alveolar stem cell populations provides fresh hope of target-directed, regenerative therapies for alveolar diseases.
TextSentencer_T56 10931-11135 Sentence denotes Cuboidal type-II pneumocytes have long been considered as progenitors of the alveolar epithelium, based on their capacity to replenish themselves and generate terminally differentiated type I pneumocytes.
TextSentencer_T56 10931-11135 Sentence denotes Cuboidal type-II pneumocytes have long been considered as progenitors of the alveolar epithelium, based on their capacity to replenish themselves and generate terminally differentiated type I pneumocytes.
TextSentencer_T57 11136-11330 Sentence denotes 34, 35 Since then, type-II pneumocytes have been speculated to contain a subpopulation of progenitors cells that can undergo reactivation into a progenitor-like state in response to injury cues.
TextSentencer_T57 11136-11330 Sentence denotes 34, 35 Since then, type-II pneumocytes have been speculated to contain a subpopulation of progenitors cells that can undergo reactivation into a progenitor-like state in response to injury cues.
TextSentencer_T58 11331-11540 Sentence denotes Using an acute model of oxygen-induced injury, Driscoll and colleagues 36 demonstrated the existence of a telomerase-positive subpopulation within the general type-II cell population during the recovery phase.
TextSentencer_T58 11331-11540 Sentence denotes Using an acute model of oxygen-induced injury, Driscoll and colleagues 36 demonstrated the existence of a telomerase-positive subpopulation within the general type-II cell population during the recovery phase.
TextSentencer_T59 11541-11792 Sentence denotes These findings were further strengthened by a later study in which Reddy and colleagues 37 classified type-II cells into E-cadherin-positive and -negative fractions, and showed heightened telomerase activity and injury resistance in the latter subset.
TextSentencer_T59 11541-11792 Sentence denotes These findings were further strengthened by a later study in which Reddy and colleagues 37 classified type-II cells into E-cadherin-positive and -negative fractions, and showed heightened telomerase activity and injury resistance in the latter subset.
TextSentencer_T60 11793-11917 Sentence denotes Additional lung cell types, including airway smooth muscle, fibroblasts, and the vasculature, are derived from the mesoderm.
TextSentencer_T60 11793-11917 Sentence denotes Additional lung cell types, including airway smooth muscle, fibroblasts, and the vasculature, are derived from the mesoderm.
TextSentencer_T61 11918-12164 Sentence denotes Interactions between the epithelial cells, mesenchymal microenvironment (including extracellular matrix proteins and growth factors), and the adjacent pulmonary vasculature regulate the structural and functional maturation of the developing lung.
TextSentencer_T61 11918-12164 Sentence denotes Interactions between the epithelial cells, mesenchymal microenvironment (including extracellular matrix proteins and growth factors), and the adjacent pulmonary vasculature regulate the structural and functional maturation of the developing lung.
TextSentencer_T62 12165-12416 Sentence denotes 21 Current knowledge of lung mesenchymal precursors is limited; however, there is evidence that small populations of resident lung cells expressing certain phenotypic characteristics of mesenchymal cells with progenitor capacity exist within the lung.
TextSentencer_T62 12165-12416 Sentence denotes 21 Current knowledge of lung mesenchymal precursors is limited; however, there is evidence that small populations of resident lung cells expressing certain phenotypic characteristics of mesenchymal cells with progenitor capacity exist within the lung.
TextSentencer_T63 12417-12791 Sentence denotes Resident lung "side population" (SP) cells, which appear to have both mesenchymal and epithelial potential, have been isolated based on their capacity to efflux Hoechst dye. [38] [39] [40] These SP cells have been shown to be present at all levels of the airway tree, and regardless of which lung compartment they were derived from, exhibited a relatively uniform phenotype.
TextSentencer_T63 12417-12791 Sentence denotes Resident lung "side population" (SP) cells, which appear to have both mesenchymal and epithelial potential, have been isolated based on their capacity to efflux Hoechst dye. [38] [39] [40] These SP cells have been shown to be present at all levels of the airway tree, and regardless of which lung compartment they were derived from, exhibited a relatively uniform phenotype.
TextSentencer_T64 12792-12986 Sentence denotes 40 Although it has been demonstrated that these SP cells are a source of adult lung mesenchymal stem cells (MSCs), 39 the role of SP cells in endogenous lung repair is not completely understood.
TextSentencer_T64 12792-12986 Sentence denotes 40 Although it has been demonstrated that these SP cells are a source of adult lung mesenchymal stem cells (MSCs), 39 the role of SP cells in endogenous lung repair is not completely understood.
TextSentencer_T65 12987-13208 Sentence denotes Furthermore, McQualter and colleagues 41 described a population of endogenous fibroblastic progenitor cells with clonogenic potential in the adult lung, which are predominantly representative of mesenchymal cell lineages.
TextSentencer_T65 12987-13208 Sentence denotes Furthermore, McQualter and colleagues 41 described a population of endogenous fibroblastic progenitor cells with clonogenic potential in the adult lung, which are predominantly representative of mesenchymal cell lineages.
TextSentencer_T66 13209-13485 Sentence denotes The cell fraction defined by McQualter and colleagues 18 was of similar cell phenotype (CD45 À , CD31 À , Sca-1 1 , CD43 1 ) to the cell fraction defined as BASCs; however, they coexpressed immunophenotypic markers definitive of lung fibroblastic rather than epithelial cells.
TextSentencer_T66 13209-13485 Sentence denotes The cell fraction defined by McQualter and colleagues 18 was of similar cell phenotype (CD45 À , CD31 À , Sca-1 1 , CD43 1 ) to the cell fraction defined as BASCs; however, they coexpressed immunophenotypic markers definitive of lung fibroblastic rather than epithelial cells.
TextSentencer_T67 13486-13656 Sentence denotes 41 These findings highlight the need for alternative, specific markers to enable precise identification of endogenous stem/progenitor cell subpopulations within the lung.
TextSentencer_T67 13486-13656 Sentence denotes 41 These findings highlight the need for alternative, specific markers to enable precise identification of endogenous stem/progenitor cell subpopulations within the lung.
TextSentencer_T68 13657-13914 Sentence denotes Following the discovery of the plasticity characteristics of ASCs that allow them to cross lineage barriers and adopt functional phenotypes of other tissues, much interest has been diverted to understanding their role in repair and maintenance of the lungs.
TextSentencer_T68 13657-13914 Sentence denotes Following the discovery of the plasticity characteristics of ASCs that allow them to cross lineage barriers and adopt functional phenotypes of other tissues, much interest has been diverted to understanding their role in repair and maintenance of the lungs.
TextSentencer_T69 13915-14078 Sentence denotes 42 Experimental evidence indicates that the injured lung stimulates the release and preferential homing of MSCs, a population of ASCs derived from the bone marrow.
TextSentencer_T69 13915-14078 Sentence denotes 42 Experimental evidence indicates that the injured lung stimulates the release and preferential homing of MSCs, a population of ASCs derived from the bone marrow.
TextSentencer_T70 14079-14240 Sentence denotes 43, 44 However, the mechanism by which exogenous progenitors, such as bone marrow MSCs, assume lung phenotype remains unclear, as does its clinical significance.
TextSentencer_T70 14079-14240 Sentence denotes 43, 44 However, the mechanism by which exogenous progenitors, such as bone marrow MSCs, assume lung phenotype remains unclear, as does its clinical significance.
TextSentencer_T71 14241-14451 Sentence denotes 45, 46 Lung Endothelial Progenitor Cells Endothelial progenitor cells (EPCs), a population of vascular precursor cells, have also recently received attention in the context of lung development and regeneration.
TextSentencer_T71 14241-14451 Sentence denotes 45, 46 Lung Endothelial Progenitor Cells Endothelial progenitor cells (EPCs), a population of vascular precursor cells, have also recently received attention in the context of lung development and regeneration.
TextSentencer_T72 14452-14662 Sentence denotes Indeed, given the importance of lung angiogenesis and vascular growth factors during lung growth and repair, vascular progenitor cells are appealing candidate cells likely to be involved in the same mechanisms.
TextSentencer_T72 14452-14662 Sentence denotes Indeed, given the importance of lung angiogenesis and vascular growth factors during lung growth and repair, vascular progenitor cells are appealing candidate cells likely to be involved in the same mechanisms.
TextSentencer_T73 14663-14918 Sentence denotes 47 However, assessment of the contribution of endogenous lung EPCs in lung vascular repair and lung regeneration and remodeling is impeded by their rarity, lack of distinguishing markers, and the inability to discriminate circulating EPCs and tissue EPCs.
TextSentencer_T73 14663-14918 Sentence denotes 47 However, assessment of the contribution of endogenous lung EPCs in lung vascular repair and lung regeneration and remodeling is impeded by their rarity, lack of distinguishing markers, and the inability to discriminate circulating EPCs and tissue EPCs.
TextSentencer_T74 14919-15218 Sentence denotes 22 Alvarez and colleagues 48 demonstrated that the lung microvasculature is enriched with a population of EPCs, termed resident microvascular endothelial progenitor cells, which were shown to be highly proliferative and capable of renewing the entire hierarchy of endothelial cell growth potentials.
TextSentencer_T74 14919-15218 Sentence denotes 22 Alvarez and colleagues 48 demonstrated that the lung microvasculature is enriched with a population of EPCs, termed resident microvascular endothelial progenitor cells, which were shown to be highly proliferative and capable of renewing the entire hierarchy of endothelial cell growth potentials.
TextSentencer_T75 15219-15370 Sentence denotes It has been demonstrated that both circulating and resident lung EPCs are likely to contribute to endothelial cell regeneration and repair in the lung.
TextSentencer_T75 15219-15370 Sentence denotes It has been demonstrated that both circulating and resident lung EPCs are likely to contribute to endothelial cell regeneration and repair in the lung.
TextSentencer_T76 15371-15599 Sentence denotes 49, 50 The recent surge in our knowledge of stem cell biology and the availability of advanced research tools in this field has motivated researchers in exploring the role of lung stem cells in the pathogenesis of lung diseases.
TextSentencer_T76 15371-15599 Sentence denotes 49, 50 The recent surge in our knowledge of stem cell biology and the availability of advanced research tools in this field has motivated researchers in exploring the role of lung stem cells in the pathogenesis of lung diseases.
TextSentencer_T77 15600-15739 Sentence denotes Indeed, several major lung diseases likely involve dysregulation in the numbers and/or the function of resident lung stem/progenitor cells.
TextSentencer_T77 15600-15739 Sentence denotes Indeed, several major lung diseases likely involve dysregulation in the numbers and/or the function of resident lung stem/progenitor cells.
TextSentencer_T78 15740-15955 Sentence denotes 46 For instance, depletion or functional impairment of alveolar epithelial and/or EPCs could putatively underlie the pathogenesis of alveolar growth arrest or destruction observed in BPD and emphysema, respectively.
TextSentencer_T78 15740-15955 Sentence denotes 46 For instance, depletion or functional impairment of alveolar epithelial and/or EPCs could putatively underlie the pathogenesis of alveolar growth arrest or destruction observed in BPD and emphysema, respectively.
TextSentencer_T79 15956-16104 Sentence denotes In such a scenario, augmentation of stem cells is an appealing strategy to minimize lung injury, promote repair, or possibly regenerate lost tissue.
TextSentencer_T79 15956-16104 Sentence denotes In such a scenario, augmentation of stem cells is an appealing strategy to minimize lung injury, promote repair, or possibly regenerate lost tissue.
TextSentencer_T80 16105-16292 Sentence denotes Recent animal and human studies suggest that damage or depletion of epithelial and/ or vascular stem/progenitor cells in the developing lung likely contributes to the pathogenesis of BPD.
TextSentencer_T80 16105-16292 Sentence denotes Recent animal and human studies suggest that damage or depletion of epithelial and/ or vascular stem/progenitor cells in the developing lung likely contributes to the pathogenesis of BPD.
TextSentencer_T81 16293-16418 Sentence denotes Exposure of neonatal rodents to high levels of oxygen is extensively used as an injury model to investigate experimental BPD.
TextSentencer_T81 16293-16418 Sentence denotes Exposure of neonatal rodents to high levels of oxygen is extensively used as an injury model to investigate experimental BPD.
TextSentencer_T82 16419-16547 Sentence denotes Irwin and colleagues 51 showed a reduction in the number and endothelial differentiation potential of multipotent lung SP cells.
TextSentencer_T82 16419-16547 Sentence denotes Irwin and colleagues 51 showed a reduction in the number and endothelial differentiation potential of multipotent lung SP cells.
TextSentencer_T83 16548-16724 Sentence denotes Observations from the authors' own laboratory in an oxygen-challenged neonatal rat model of BPD have also shown decreased numbers of circulating and resident MSCs in the lungs.
TextSentencer_T83 16548-16724 Sentence denotes Observations from the authors' own laboratory in an oxygen-challenged neonatal rat model of BPD have also shown decreased numbers of circulating and resident MSCs in the lungs.
TextSentencer_T84 16725-16848 Sentence denotes 52 This finding highlights the potential of stem cell supplementation for the prevention or repair of neonatal lung injury.
TextSentencer_T84 16725-16848 Sentence denotes 52 This finding highlights the potential of stem cell supplementation for the prevention or repair of neonatal lung injury.
TextSentencer_T85 16849-17003 Sentence denotes Accordingly, systemic treatment of neonatal hyperoxia-exposed mice with MSCs significantly increases the number of BASCs compared with untreated controls.
TextSentencer_T85 16849-17003 Sentence denotes Accordingly, systemic treatment of neonatal hyperoxia-exposed mice with MSCs significantly increases the number of BASCs compared with untreated controls.
TextSentencer_T86 17004-17167 Sentence denotes In addition, treatment of BASCs with MSC-derived conditioned media (CdM) in culture stimulated BASC growth efficiency, indicating a direct effect of MSCs on BASCs.
TextSentencer_T86 17004-17167 Sentence denotes In addition, treatment of BASCs with MSC-derived conditioned media (CdM) in culture stimulated BASC growth efficiency, indicating a direct effect of MSCs on BASCs.
TextSentencer_T87 17168-17411 Sentence denotes 53 In contrast to the aforementioned reports of depleted numbers of stem/progenitor cells, Popova and colleagues 54 demonstrated that the presence of MSCs in tracheal aspirates of preterm infants indicated an increased risk for developing BPD.
TextSentencer_T87 17168-17411 Sentence denotes 53 In contrast to the aforementioned reports of depleted numbers of stem/progenitor cells, Popova and colleagues 54 demonstrated that the presence of MSCs in tracheal aspirates of preterm infants indicated an increased risk for developing BPD.
TextSentencer_T88 17412-17629 Sentence denotes Those cells isolated from the tracheal aspirates expressed the markers STRO-1, CD73, CD90, CD105, CD166, CCR2b, CD13, propyl-4-hydroxylase, and a-smooth muscle actin, and were negative for CD11b, CD31, CD34, and CD45.
TextSentencer_T88 17412-17629 Sentence denotes Those cells isolated from the tracheal aspirates expressed the markers STRO-1, CD73, CD90, CD105, CD166, CCR2b, CD13, propyl-4-hydroxylase, and a-smooth muscle actin, and were negative for CD11b, CD31, CD34, and CD45.
TextSentencer_T89 17630-17811 Sentence denotes 55 Furthermore, these cells were shown to acquire a myofibroblast phenotype, which suggest that they could contribute to the profibrotic changes and arrested alveolarization in BPD.
TextSentencer_T89 17630-17811 Sentence denotes 55 Furthermore, these cells were shown to acquire a myofibroblast phenotype, which suggest that they could contribute to the profibrotic changes and arrested alveolarization in BPD.
TextSentencer_T90 17812-18097 Sentence denotes 56 However, in contrast to tracheal aspirate MSCs, human bone marrow-derived MSCs did not Stem Cells and Bronchopulmonary Dysplasia undergo myofibroblastic differentiation in response to transforming growth factor b1, suggesting distinct properties between these 2 populations of MSCs.
TextSentencer_T90 17812-18097 Sentence denotes 56 However, in contrast to tracheal aspirate MSCs, human bone marrow-derived MSCs did not Stem Cells and Bronchopulmonary Dysplasia undergo myofibroblastic differentiation in response to transforming growth factor b1, suggesting distinct properties between these 2 populations of MSCs.
TextSentencer_T91 18098-18320 Sentence denotes 56 Indeed, it is possible that these reported resident lung MSCs are perturbed in BPD, as their cell phenotype is not analogous to the endogenous MSCs described by McQualter and colleagues 41 in the absence of lung injury.
TextSentencer_T91 18098-18320 Sentence denotes 56 Indeed, it is possible that these reported resident lung MSCs are perturbed in BPD, as their cell phenotype is not analogous to the endogenous MSCs described by McQualter and colleagues 41 in the absence of lung injury.
TextSentencer_T92 18321-18728 Sentence denotes Therefore, with the growing interest in harnessing the therapeutic effects of stem progenitor cells for neonatal lung injury, it is necessary to perform further thorough investigations to understand the behavior of MSCs from different populations (ie, lung, umbilical cord blood [UCB], bone marrow) in the presence and absence of lung injury, and how this could affect potential cellbased therapies for BPD.
TextSentencer_T92 18321-18728 Sentence denotes Therefore, with the growing interest in harnessing the therapeutic effects of stem progenitor cells for neonatal lung injury, it is necessary to perform further thorough investigations to understand the behavior of MSCs from different populations (ie, lung, umbilical cord blood [UCB], bone marrow) in the presence and absence of lung injury, and how this could affect potential cellbased therapies for BPD.
TextSentencer_T93 18729-18731 Sentence denotes 57
TextSentencer_T93 18729-18731 Sentence denotes 57
TextSentencer_T94 18732-18878 Sentence denotes Neonatal mice with oxygen-induced chronic lung injury have depleted numbers of putative lung-resident EPCs (CD45 À /Sca-1 1 /CD133 1 /VEGFR-2 1 ).
TextSentencer_T94 18732-18878 Sentence denotes Neonatal mice with oxygen-induced chronic lung injury have depleted numbers of putative lung-resident EPCs (CD45 À /Sca-1 1 /CD133 1 /VEGFR-2 1 ).
TextSentencer_T95 18879-19072 Sentence denotes 50 Baker and colleagues 58 demonstrated that UCB of preterm infants yielded a higher amount of endothelial colony-forming cells (ECFCs; a specific subset of EPCs) than from UCB of term infants.
TextSentencer_T95 18879-19072 Sentence denotes 50 Baker and colleagues 58 demonstrated that UCB of preterm infants yielded a higher amount of endothelial colony-forming cells (ECFCs; a specific subset of EPCs) than from UCB of term infants.
TextSentencer_T96 19073-19163 Sentence denotes Preterm ECFCs had an increased susceptibility to in vitro oxygen exposure than term ECFCs.
TextSentencer_T96 19073-19163 Sentence denotes Preterm ECFCs had an increased susceptibility to in vitro oxygen exposure than term ECFCs.
TextSentencer_T97 19164-19350 Sentence denotes 58 Borghesi and colleagues 59 reported that the number of ECFCs was lower in UCB of preterm infants who subsequently developed BPD, compared with preterm infants who did not develop BPD.
TextSentencer_T97 19164-19350 Sentence denotes 58 Borghesi and colleagues 59 reported that the number of ECFCs was lower in UCB of preterm infants who subsequently developed BPD, compared with preterm infants who did not develop BPD.
TextSentencer_T98 19351-19544 Sentence denotes In contrast to the findings of Borghesi and colleagues, 59 Paviotti and colleagues 60 recently reported no association between the number of EPCs at birth and the subsequent development of BPD.
TextSentencer_T98 19351-19544 Sentence denotes In contrast to the findings of Borghesi and colleagues, 59 Paviotti and colleagues 60 recently reported no association between the number of EPCs at birth and the subsequent development of BPD.
TextSentencer_T99 19545-19763 Sentence denotes The apparent discordance between studies reporting EPCs in preterm infants highlights the importance of appropriately defining an EPC and establishing criteria similar to the "minimal criteria" for characterizing MSCs.
TextSentencer_T99 19545-19763 Sentence denotes The apparent discordance between studies reporting EPCs in preterm infants highlights the importance of appropriately defining an EPC and establishing criteria similar to the "minimal criteria" for characterizing MSCs.
TextSentencer_T100 19764-19851 Sentence denotes 61 Furthermore, assessing EPC function may be more revealing than assessing EPC number.
TextSentencer_T100 19764-19851 Sentence denotes 61 Furthermore, assessing EPC function may be more revealing than assessing EPC number.
TextSentencer_T101 19852-20067 Sentence denotes These observations suggest that the capacity of resident stem cell populations to undergo self-renewal and regeneration can be limited, because of the natural effect of increasing age and/or the presence of disease.
TextSentencer_T101 19852-20067 Sentence denotes These observations suggest that the capacity of resident stem cell populations to undergo self-renewal and regeneration can be limited, because of the natural effect of increasing age and/or the presence of disease.
TextSentencer_T102 20068-20286 Sentence denotes This situation forms the rationale for the therapeutic potential of stem cell-based therapies, either through stimulation of endogenous stem cell pools or their therapeutic replacement with exogenousderived stem cells.
TextSentencer_T102 20068-20286 Sentence denotes This situation forms the rationale for the therapeutic potential of stem cell-based therapies, either through stimulation of endogenous stem cell pools or their therapeutic replacement with exogenousderived stem cells.
TextSentencer_T103 20287-20518 Sentence denotes Such cell-replacement therapies already show promise in debilitating childhood and adult disorders. [62] [63] [64] In the laboratory, stem cell-based strategies have shown therapeutic benefit in experimental models of lung disease.
TextSentencer_T103 20287-20518 Sentence denotes Such cell-replacement therapies already show promise in debilitating childhood and adult disorders. [62] [63] [64] In the laboratory, stem cell-based strategies have shown therapeutic benefit in experimental models of lung disease.
TextSentencer_T104 20519-21040 Sentence denotes Numerous studies in experimental animal models provide compelling evidence for the beneficial effects of stem cell therapy approaches for a wide variety of adult lung diseases ( Table 2) , including acute lung injury/acute respiratory distress syndrome, pulmonary hypertension, asthma, and chronic obstructive pulmonary disease (including emphysema). [65] [66] [67] Of the many different stem/progenitor cell therapies that have been used in experimental models, MSCs appear to be the most extensively examined cell type.
TextSentencer_T104 20519-21040 Sentence denotes Numerous studies in experimental animal models provide compelling evidence for the beneficial effects of stem cell therapy approaches for a wide variety of adult lung diseases ( Table 2) , including acute lung injury/acute respiratory distress syndrome, pulmonary hypertension, asthma, and chronic obstructive pulmonary disease (including emphysema). [65] [66] [67] Of the many different stem/progenitor cell therapies that have been used in experimental models, MSCs appear to be the most extensively examined cell type.
TextSentencer_T105 21041-21136 Sentence denotes MSCs can be sourced from the bone marrow, UCB, Wharton jelly, the placenta, and adipose tissue.
TextSentencer_T105 21041-21136 Sentence denotes MSCs can be sourced from the bone marrow, UCB, Wharton jelly, the placenta, and adipose tissue.
TextSentencer_T106 21137-21476 Sentence denotes 68 As outlined in Table 2 benefits of MSC therapy in experimental adult lung diseases include, but are not limited to, improvements in alveolar, airway, and vascular structure; attenuation of lung inflammation; decreased pulmonary fibrosis; reduced pulmonary edema, hemorrhage, and alveolar and endothelial permeability; and Abbreviations:
TextSentencer_T106 21137-21476 Sentence denotes 68 As outlined in Table 2 benefits of MSC therapy in experimental adult lung diseases include, but are not limited to, improvements in alveolar, airway, and vascular structure; attenuation of lung inflammation; decreased pulmonary fibrosis; reduced pulmonary edema, hemorrhage, and alveolar and endothelial permeability; and Abbreviations:
TextSentencer_T107 21477-22629 Sentence denotes Ang-1, angiopoietin-1; APN, adiponectin; AT1, alveolar epithelial type 1; AT2, alveolar epithelial type 2; BMC, bone marrow-derived cells; CdM, conditioned media; EGF, epidermal growth factor; eNOS, endothelial nitric oxide synthase; EPC, endothelial progenitor cell; HGF, hepatocyte growth factor; HSC, hematopoietic stem cell; hAEC, human amnion epithelial cell; hUC, human umbilical cord; hUCB, human umbilical cord blood; IL, interleukin; i.n., intranasal; i.p., intraperitoneal; iPS, induced pluripotent stem; i.t., intratracheal; i.v., intravenous; KGF, keratinocyte growth factor; LPS, lipopolysaccharide; LVRS, lung volume reduction surgery; MMP-2, matrix metalloproteinase 2; MPO, myeloperoxidase; MSC, mesenchymal stem cell; NF-kB, nuclear factor kappa light-chain enhancer of activated B cells; NO, nitric oxide; PaO 2 , partial pressure of oxygen in arterial blood; PGA, polyglycolic acid; RV, right ventricle; SaO 2 , oxygen saturation; TGF-b, transforming growth factor b; Th2, helper T cell type 2; TIMP, tissue inhibitor of metalloproteinase; VEGF, vascular endothelial growth factor. restoration of lung function and exercise capacity.
TextSentencer_T107 21477-22629 Sentence denotes Ang-1, angiopoietin-1; APN, adiponectin; AT1, alveolar epithelial type 1; AT2, alveolar epithelial type 2; BMC, bone marrow-derived cells; CdM, conditioned media; EGF, epidermal growth factor; eNOS, endothelial nitric oxide synthase; EPC, endothelial progenitor cell; HGF, hepatocyte growth factor; HSC, hematopoietic stem cell; hAEC, human amnion epithelial cell; hUC, human umbilical cord; hUCB, human umbilical cord blood; IL, interleukin; i.n., intranasal; i.p., intraperitoneal; iPS, induced pluripotent stem; i.t., intratracheal; i.v., intravenous; KGF, keratinocyte growth factor; LPS, lipopolysaccharide; LVRS, lung volume reduction surgery; MMP-2, matrix metalloproteinase 2; MPO, myeloperoxidase; MSC, mesenchymal stem cell; NF-kB, nuclear factor kappa light-chain enhancer of activated B cells; NO, nitric oxide; PaO 2 , partial pressure of oxygen in arterial blood; PGA, polyglycolic acid; RV, right ventricle; SaO 2 , oxygen saturation; TGF-b, transforming growth factor b; Th2, helper T cell type 2; TIMP, tissue inhibitor of metalloproteinase; VEGF, vascular endothelial growth factor. restoration of lung function and exercise capacity.
TextSentencer_T108 22630-22830 Sentence denotes Of importance, the beneficial therapeutic actions of MSCs appear to be mediated through paracrine mechanisms and immunomodulatory effects, rather than cell engraftment and direct actions in the lungs.
TextSentencer_T108 22630-22830 Sentence denotes Of importance, the beneficial therapeutic actions of MSCs appear to be mediated through paracrine mechanisms and immunomodulatory effects, rather than cell engraftment and direct actions in the lungs.
TextSentencer_T109 22831-22995 Sentence denotes 69 The use of MSCs and other types of stem/progenitor cells are also being increasingly examined in experimental models of neonatal lung disease, in particular BPD.
TextSentencer_T109 22831-22995 Sentence denotes 69 The use of MSCs and other types of stem/progenitor cells are also being increasingly examined in experimental models of neonatal lung disease, in particular BPD.
TextSentencer_T110 22996-23239 Sentence denotes Given the perturbations of resident lung stem cells in BPD, the ideal therapeutic approach would involve replenishing the lung with healthy multipotent stem/progenitor cells that repopulate, repair, and regenerate the injured, developing lung.
TextSentencer_T110 22996-23239 Sentence denotes Given the perturbations of resident lung stem cells in BPD, the ideal therapeutic approach would involve replenishing the lung with healthy multipotent stem/progenitor cells that repopulate, repair, and regenerate the injured, developing lung.
TextSentencer_T111 23240-23395 Sentence denotes Indeed, several recent studies have demonstrated promising outcomes using different stem/ progenitor cell types in animal models of BPD (Fig. 2, Table 3 ).
TextSentencer_T111 23240-23395 Sentence denotes Indeed, several recent studies have demonstrated promising outcomes using different stem/ progenitor cell types in animal models of BPD (Fig. 2, Table 3 ).
TextSentencer_T112 23396-23747 Sentence denotes Administration of bone marrow-derived MSCs, either intratracheally, intravenously, or intraperitoneally, have ameliorated numerous aspects of neonatal lung injury, as evident by mitigation of lung inflammation, prevention of lung vascular damage and alveolar growth arrest, inhibition of lung fibrosis, and improvement in exercise tolerance (Fig. 3) .
TextSentencer_T112 23396-23747 Sentence denotes Administration of bone marrow-derived MSCs, either intratracheally, intravenously, or intraperitoneally, have ameliorated numerous aspects of neonatal lung injury, as evident by mitigation of lung inflammation, prevention of lung vascular damage and alveolar growth arrest, inhibition of lung fibrosis, and improvement in exercise tolerance (Fig. 3) .
TextSentencer_T113 23748-23944 Sentence denotes 52, 53, 70, 71 Low engraftment and differentiation of these MSCs into the injured neonatal lung suggest that the potential mechanisms through which MSCs exert their actions are paracrine mediated.
TextSentencer_T113 23748-23944 Sentence denotes 52, 53, 70, 71 Low engraftment and differentiation of these MSCs into the injured neonatal lung suggest that the potential mechanisms through which MSCs exert their actions are paracrine mediated.
TextSentencer_T114 23945-24304 Sentence denotes These speculations are supported by in vitro and in vivo studies demonstrating that administration of CdM from MSCs has the ability to protect alveolar epithelial and lung microvascular endothelial cells from oxidative stress, prevent oxygen-induced alveolar growth arrest, and stimulate a subset of stem/progenitor cells, namely BASCs, to aid in lung repair.
TextSentencer_T114 23945-24304 Sentence denotes These speculations are supported by in vitro and in vivo studies demonstrating that administration of CdM from MSCs has the ability to protect alveolar epithelial and lung microvascular endothelial cells from oxidative stress, prevent oxygen-induced alveolar growth arrest, and stimulate a subset of stem/progenitor cells, namely BASCs, to aid in lung repair.
TextSentencer_T115 24305-24413 Sentence denotes 52, 53, 70 Furthermore, the therapeutic benefits of MSC-CdM may surpass those of MSCs, with in vivo Fig. 2 .
TextSentencer_T115 24305-24413 Sentence denotes 52, 53, 70 Furthermore, the therapeutic benefits of MSC-CdM may surpass those of MSCs, with in vivo Fig. 2 .
TextSentencer_T116 24414-24524 Sentence denotes Current sources of stem/progenitor cells for lung regeneration in experimental models of neonatal lung injury.
TextSentencer_T116 24414-24524 Sentence denotes Current sources of stem/progenitor cells for lung regeneration in experimental models of neonatal lung injury.
TextSentencer_T117 24525-24752 Sentence denotes Several studies have demonstrated the effects of stem/progenitor cells and stem/progenitor cell-derived growth factors (ie, conditioned media) to promote lung regeneration following neonatal lung injury in animal models of BPD.
TextSentencer_T117 24525-24752 Sentence denotes Several studies have demonstrated the effects of stem/progenitor cells and stem/progenitor cell-derived growth factors (ie, conditioned media) to promote lung regeneration following neonatal lung injury in animal models of BPD.
TextSentencer_T118 24753-24967 Sentence denotes These cells were sourced from the bone marrow, umbilical cord blood, and placenta amnion. findings indicating a more profound therapeutic effect of MSC-CdM in preventing and repairing lung injury than that of MSCs.
TextSentencer_T118 24753-24967 Sentence denotes These cells were sourced from the bone marrow, umbilical cord blood, and placenta amnion. findings indicating a more profound therapeutic effect of MSC-CdM in preventing and repairing lung injury than that of MSCs.
TextSentencer_T119 24968-25181 Sentence denotes 70 UCB also represents an appealing source of MSCs for therapeutic use in the newborn because of its clinically relevant, easily accessible, ethically viable, and readily available source of stem/progenitor cells.
TextSentencer_T119 24968-25181 Sentence denotes 70 UCB also represents an appealing source of MSCs for therapeutic use in the newborn because of its clinically relevant, easily accessible, ethically viable, and readily available source of stem/progenitor cells.
TextSentencer_T120 25182-25375 Sentence denotes Chang and colleagues 72,73 demonstrated that MSCs obtained from human UCB prevent hyperoxia-induced alveolar growth arrest and alleviate fibrotic changes in the neonatal rat lung (see Fig. 3 ).
TextSentencer_T120 25182-25375 Sentence denotes Chang and colleagues 72,73 demonstrated that MSCs obtained from human UCB prevent hyperoxia-induced alveolar growth arrest and alleviate fibrotic changes in the neonatal rat lung (see Fig. 3 ).
TextSentencer_T121 25376-25613 Sentence denotes Chang and colleagues 73 also show that the route of administration may alter the outcome, with intratracheal transplantation resulting in a more prominent attenuation of hyperoxia-induced lung injury than intraperitoneal transplantation.
TextSentencer_T121 25376-25613 Sentence denotes Chang and colleagues 73 also show that the route of administration may alter the outcome, with intratracheal transplantation resulting in a more prominent attenuation of hyperoxia-induced lung injury than intraperitoneal transplantation.
TextSentencer_T122 25614-25769 Sentence denotes Furthermore, Chang and colleagues 72 recently demonstrated the dose-dependent effects of human UCB-derived MSCs in the oxygen-challenged neonatal rat lung.
TextSentencer_T122 25614-25769 Sentence denotes Furthermore, Chang and colleagues 72 recently demonstrated the dose-dependent effects of human UCB-derived MSCs in the oxygen-challenged neonatal rat lung.
TextSentencer_T123 25770-25999 Sentence denotes This study indicated that intratracheal delivery of a minimum of 5 Â 10 4 cells is required to exhibit efficient anti-inflammatory, antifibrotic, and antioxidative effects following hyperoxia-induced lung injury in neonatal rats.
TextSentencer_T123 25770-25999 Sentence denotes This study indicated that intratracheal delivery of a minimum of 5 Â 10 4 cells is required to exhibit efficient anti-inflammatory, antifibrotic, and antioxidative effects following hyperoxia-induced lung injury in neonatal rats.
TextSentencer_T124 26000-26149 Sentence denotes 72 In light of these findings, further studies determining the optimal dose of MSCs for potential clinical benefit in human neonates are anticipated.
TextSentencer_T124 26000-26149 Sentence denotes 72 In light of these findings, further studies determining the optimal dose of MSCs for potential clinical benefit in human neonates are anticipated.
TextSentencer_T125 26150-26279 Sentence denotes The therapeutic potential of EPCs in neonatal lung injury has been effectively demonstrated in an oxygen-induced BPD mouse model.
TextSentencer_T125 26150-26279 Sentence denotes The therapeutic potential of EPCs in neonatal lung injury has been effectively demonstrated in an oxygen-induced BPD mouse model.
TextSentencer_T126 26280-26568 Sentence denotes 74 Treatment of neonatal mice exposed to hyperoxia with intravenously administered bone marrow-derived angiogenic cells (a population of bone marrow myeloid-like precursor cells) showed restoration of the alveolar structure and vessel density to that of control (room air-exposed) levels.
TextSentencer_T126 26280-26568 Sentence denotes 74 Treatment of neonatal mice exposed to hyperoxia with intravenously administered bone marrow-derived angiogenic cells (a population of bone marrow myeloid-like precursor cells) showed restoration of the alveolar structure and vessel density to that of control (room air-exposed) levels.
TextSentencer_T127 26569-26571 Sentence denotes 74
TextSentencer_T127 26569-26571 Sentence denotes 74
TextSentencer_T128 26573-26779 Sentence denotes The therapeutic potential of human amnion epithelial cells (hAECs) has recently been investigated in a sheep model of neonatal lung injury, induced by lipopolysaccharide (LPS) administration in fetal sheep.
TextSentencer_T128 26573-26779 Sentence denotes The therapeutic potential of human amnion epithelial cells (hAECs) has recently been investigated in a sheep model of neonatal lung injury, induced by lipopolysaccharide (LPS) administration in fetal sheep.
TextSentencer_T129 26780-26949 Sentence denotes 75 Because hAECs are sourced from placentae, which are normally discarded after birth, they present an easily accessible and ethically viable candidate for cell therapy.
TextSentencer_T129 26780-26949 Sentence denotes 75 Because hAECs are sourced from placentae, which are normally discarded after birth, they present an easily accessible and ethically viable candidate for cell therapy.
TextSentencer_T130 26950-27111 Sentence denotes Administration of hAECs to fetal sheep exposed to LPS attenuated inflammation-induced changes in lung function and structure, and reduced pulmonary inflammation.
TextSentencer_T130 26950-27111 Sentence denotes Administration of hAECs to fetal sheep exposed to LPS attenuated inflammation-induced changes in lung function and structure, and reduced pulmonary inflammation.
TextSentencer_T131 27112-27227 Sentence denotes 75 Of particular interest is the ability of hAECs to significantly increase the expression levels of SP-A and SP-C.
TextSentencer_T131 27112-27227 Sentence denotes 75 Of particular interest is the ability of hAECs to significantly increase the expression levels of SP-A and SP-C.
TextSentencer_T132 27228-27365 Sentence denotes The low engraftment into the lungs indicates that these hAECs act via immune modulation rather than cell engraftment and differentiation.
TextSentencer_T132 27228-27365 Sentence denotes The low engraftment into the lungs indicates that these hAECs act via immune modulation rather than cell engraftment and differentiation.
TextSentencer_T133 27366-27495 Sentence denotes More detailed assessment of the therapeutic potential of these cells in other models of neonatal lung injury will be of interest.
TextSentencer_T133 27366-27495 Sentence denotes More detailed assessment of the therapeutic potential of these cells in other models of neonatal lung injury will be of interest.
TextSentencer_T134 27496-27671 Sentence denotes In summary, findings from several exciting studies indicate that a variety of stem/ progenitor cells can prevent and/or regenerate neonatal lung injury in experimental models.
TextSentencer_T134 27496-27671 Sentence denotes In summary, findings from several exciting studies indicate that a variety of stem/ progenitor cells can prevent and/or regenerate neonatal lung injury in experimental models.
TextSentencer_T135 27672-27844 Sentence denotes Additional studies in different animal models of BPD are necessary to broaden the current knowledge and understanding of the therapeutic potential of stem/progenitor cells.
TextSentencer_T135 27672-27844 Sentence denotes Additional studies in different animal models of BPD are necessary to broaden the current knowledge and understanding of the therapeutic potential of stem/progenitor cells.
TextSentencer_T136 27845-27982 Sentence denotes In doing so, further evidence for creating a strong rationale for transitioning this potential breakthrough into clinic can be generated.
TextSentencer_T136 27845-27982 Sentence denotes In doing so, further evidence for creating a strong rationale for transitioning this potential breakthrough into clinic can be generated.
TextSentencer_T137 27983-28210 Sentence denotes Although stem/progenitor cell therapies present potential promise in preventing and/or repairing lung injury, many gaps in our knowledge and understanding of stem cell biology in health and disease are yet to be filled (Box 1).
TextSentencer_T137 27983-28210 Sentence denotes Although stem/progenitor cell therapies present potential promise in preventing and/or repairing lung injury, many gaps in our knowledge and understanding of stem cell biology in health and disease are yet to be filled (Box 1).
TextSentencer_T138 28211-28287 Sentence denotes In part, it is important to more precisely define putative reparative cells.
TextSentencer_T138 28211-28287 Sentence denotes In part, it is important to more precisely define putative reparative cells.
TextSentencer_T139 28288-28483 Sentence denotes One of the obstacles is the lack of biomarkers available for the characterization of candidate stem/progenitor cells in different species 22 and the inability to easily study these cells in vivo.
TextSentencer_T139 28288-28483 Sentence denotes One of the obstacles is the lack of biomarkers available for the characterization of candidate stem/progenitor cells in different species 22 and the inability to easily study these cells in vivo.
TextSentencer_T140 28484-28615 Sentence denotes Current studies elegantly detail the short-term effects of stem/progenitor cell therapies in animal models of neonatal lung injury.
TextSentencer_T140 28484-28615 Sentence denotes Current studies elegantly detail the short-term effects of stem/progenitor cell therapies in animal models of neonatal lung injury.
TextSentencer_T141 28616-28925 Sentence denotes 52, 53, [70] [71] [72] [73] [74] [75] However, few of these studies have reported the long-term outcomes (ie, in mid-adult or aged lung) of such stem/ progenitor cell therapies, 52, 71 which is a vital and clinically important area of research that needs to be understood to warrant safe clinical translation.
TextSentencer_T141 28616-28925 Sentence denotes 52, 53, [70] [71] [72] [73] [74] [75] However, few of these studies have reported the long-term outcomes (ie, in mid-adult or aged lung) of such stem/ progenitor cell therapies, 52, 71 which is a vital and clinically important area of research that needs to be understood to warrant safe clinical translation.
TextSentencer_T142 28926-29274 Sentence denotes In addition, it would be valuable to understand the effects of such stem/progenitor cell therapies in other animal models of neonatal lung injury closely mimicking the clinical setting (ie, ventilator-induced, fetal/neonatal inflammation-induced), rather than the frequently used hyperoxia-induced model; indeed, this is already being used by some.
TextSentencer_T142 28926-29274 Sentence denotes In addition, it would be valuable to understand the effects of such stem/progenitor cell therapies in other animal models of neonatal lung injury closely mimicking the clinical setting (ie, ventilator-induced, fetal/neonatal inflammation-induced), rather than the frequently used hyperoxia-induced model; indeed, this is already being used by some.
TextSentencer_T143 29275-29505 Sentence denotes 75 Current studies highlight the beneficial effects of stem/progenitor cell therapy on attenuating structural and/or molecular alterations to the injured developing lung, yet the effects on lung function are infrequently reported.
TextSentencer_T143 29275-29505 Sentence denotes 75 Current studies highlight the beneficial effects of stem/progenitor cell therapy on attenuating structural and/or molecular alterations to the injured developing lung, yet the effects on lung function are infrequently reported.
TextSentencer_T144 29506-29775 Sentence denotes 52 This aspect of experimental studies requires further investigation and thorough documentation, because Stem Cells and Bronchopulmonary Dysplasia the overall aim of treating neonatal lung injury with stem/progenitor cells is to reduce and/or prevent lung dysfunction.
TextSentencer_T144 29506-29775 Sentence denotes 52 This aspect of experimental studies requires further investigation and thorough documentation, because Stem Cells and Bronchopulmonary Dysplasia the overall aim of treating neonatal lung injury with stem/progenitor cells is to reduce and/or prevent lung dysfunction.
TextSentencer_T145 29776-30077 Sentence denotes Half a century since the landmark discovery of stem cells by the Canadian researchers Till and McCulloch in 1961, 76 their therapeutic potential in regenerative medicine is now being harnessed for treatment of neonatal lung injury, almost half a century since Northway and colleagues 77 described BPD.
TextSentencer_T145 29776-30077 Sentence denotes Half a century since the landmark discovery of stem cells by the Canadian researchers Till and McCulloch in 1961, 76 their therapeutic potential in regenerative medicine is now being harnessed for treatment of neonatal lung injury, almost half a century since Northway and colleagues 77 described BPD.
TextSentencer_T146 30078-30289 Sentence denotes Various types of stem/progenitor cells have shown benefit in experimental models of neonatal lung injury, with MSCs derived from both bone marrow and UCB being popularly studied, as well as CdM from these cells.
TextSentencer_T146 30078-30289 Sentence denotes Various types of stem/progenitor cells have shown benefit in experimental models of neonatal lung injury, with MSCs derived from both bone marrow and UCB being popularly studied, as well as CdM from these cells.
TextSentencer_T147 30290-30462 Sentence denotes However, before safe clinical translation of cell-based therapies is warranted, we must broaden our knowledge and understanding in this novel and exciting area of research.
TextSentencer_T147 30290-30462 Sentence denotes However, before safe clinical translation of cell-based therapies is warranted, we must broaden our knowledge and understanding in this novel and exciting area of research.
TextSentencer_T148 30463-30627 Sentence denotes Strong emphasis must be placed on developing and standardizing techniques for stem/progenitor cell definition, isolation, expansion, and therapeutic administration.
TextSentencer_T148 30463-30627 Sentence denotes Strong emphasis must be placed on developing and standardizing techniques for stem/progenitor cell definition, isolation, expansion, and therapeutic administration.
TextSentencer_T149 30628-30712 Sentence denotes Experimental studies also need to focus on the long-term outcomes of such therapies.
TextSentencer_T149 30628-30712 Sentence denotes Experimental studies also need to focus on the long-term outcomes of such therapies.
TextSentencer_T150 30713-31040 Sentence denotes By identifying the most appropriate reparative cell(s) and its source, combined with understanding alternative mechanisms of action beyond cell replacement and assessing the short-term and long-term efficacy and safety, we can advance in the quest of providing therapeutic strategies to prevent and repair neonatal lung injury.
TextSentencer_T150 30713-31040 Sentence denotes By identifying the most appropriate reparative cell(s) and its source, combined with understanding alternative mechanisms of action beyond cell replacement and assessing the short-term and long-term efficacy and safety, we can advance in the quest of providing therapeutic strategies to prevent and repair neonatal lung injury.