Developmental Aspects of the Upper Airway: Report from an NHLBI Workshop, March 5-6, 2009

Marcus, Carole L.; Smith, Richard J.H.; Mankarious, Leila A.; Arens, Raanan; Mitchell, Gordon S.; Elluru, Ravindhra G.; Forte, Vito; Goudy, Steven L.; Jabs, Ethylin Wang; Kane, Alex A.; Katz, Eliot S.; Paydarfar, David; Pereira, Kevin D.; Reeves, Roger H.; Richtsmeier, Joan T.; Ruiz, Ramon L.; Thach, Bradley T.; Tunkel, David E.; Whitsett, Jeffrey A.; Wootton, David; Blaisdell, Carol J.

doi:10.1513/pats.200905-024cb

Cited by 26 publications

(13 citation statements)

References 62 publications

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“…( f ) Quantification of endothelial coverage in EC-, EC–ASC-, and EC–ASC–FGF9-regenerated lungs after 8 days in culture. All values are means ± standard deviation 54 of three independent experiments. P = 0.0554 (ANOVA); P = 0.1767 (Kruskal–Wallis test).…”

Section: Resultsmentioning

confidence: 99%

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Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells

Doi

Tsuchiya

Mitsutake

et al. 2017

Sci Rep

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Bioengineered lungs consisting of a decellularized lung scaffold that is repopulated with a patient’s own cells could provide desperately needed donor organs in the future. This approach has been tested in rats, and has been partially explored in porcine and human lungs. However, existing bioengineered lungs are fragile, in part because of their immature vascular structure. Herein, we report the application of adipose-derived stem/stromal cells (ASCs) for engineering the pulmonary vasculature in a decellularized rat lung scaffold. We found that pre-seeded ASCs differentiated into pericytes and stabilized the endothelial cell (EC) monolayer in nascent pulmonary vessels, thereby contributing to EC survival in the regenerated lungs. The ASC-mediated stabilization of the ECs clearly reduced vascular permeability and suppressed alveolar hemorrhage in an orthotopic transplant model for up to 3 h after extubation. Fibroblast growth factor 9, a mesenchyme-targeting growth factor, enhanced ASC differentiation into pericytes but overstimulated their proliferation, causing a partial obstruction of the vasculature in the regenerated lung. ASCs may therefore provide a promising cell source for vascular regeneration in bioengineered lungs, though additional work is needed to optimize the growth factor or hormone milieu for organ culture.

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Section: Resultsmentioning

confidence: 99%

“…Numerical values are presented as the means ± standard deviation 54 . Because the sample sizes were too small to assess normality of distribution (N = 3), both parametric and non-parametric tests were performed.…”

Section: Methodsmentioning

confidence: 99%

Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells

Doi

Tsuchiya

Mitsutake

et al. 2017

Sci Rep

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“…Could the epithelium be the site of the origins of asthma? Epithelial patterning in early life involving such transcription factors as SOX2 and may well be the reason why asthma is largely restricted to the conducting airways and does not lead to an alveolitis [121]. Placing the epithelium and underlying structural cells rather than the T lymphocyte at the centre of asthma pathogenesis helps to identify novel therapeutic targets that are more to do with protecting the airways from environmental insults rather than suppressing aspects of inflammation.…”

Section: Concluding Commentsmentioning

confidence: 99%

Asthma: a simple concept but in reality a complex disease

Holgate

2011

Eur J Clin Investigation

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Background Asthma is a disorder of the conducting airways that contract too easily and too much to cause variable airflow obstruction with symptoms of wheeze, cough, chest tightness and shortness of breath. Based on this knowledge, initial treatments were directed to dilating the contracted airways with anticholinergic and adrenergic drugs. The recognition that allergic-type inflammation underlay the hyperresponsive airways in asthma led to the introduction of anti-inflammatory drugs such as sodium cromoglicate and corticosteroids. Over the 2 decades that followed, these drugs have been progressively improved by increasing their therapeutic index and duration of action.

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“…However, we do not yet know which inflammatory molecules may be responsible for these effects. It is essential to understand mechanisms whereby inflammation could disrupt respiratory rhythm generation, since infection and inflammation are implicated in apnea of prematurity and in devastating examples of respiratory arrest, such as sudden infant death syndrome (Blackwell et al, 2005, Blood-Siegfried, 2009, Marcus et al, 2009, Dale-Nagle et al, 2010). …”

Section: Inflammation and Respiratory Rhythm Generationmentioning

confidence: 99%

Systemic inflammation impairs respiratory chemoreflexes and plasticity

Huxtable¹,

Vinit²,

Windelborn³

et al. 2011

Respiratory Physiology & Neurobiology

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Many lung and central nervous system disorders require robust and appropriate physiological responses to assure adequate breathing. Factors undermining the efficacy of ventilatory control will diminish the ability to compensate for pathology, threatening life itself. Although most of these same disorders are associated with systemic and/or neuroinflammation, and inflammation affects neural function, we are only beginning to understand interactions between inflammation and any aspect of ventilatory control (e.g. sensory receptors, rhythm generation, chemoreflexes, plasticity). Here we review available evidence, and present limited new data suggesting that systemic (or neural) inflammation impairs two key elements of ventilatory control: chemoreflexes and respiratory motor (vs. sensory) plasticity. Achieving an understanding of mechanisms whereby inflammation undermines ventilatory control is fundamental since inflammation may diminish the capacity for natural, compensatory responses during pathological states, and the ability to harness respiratory plasticity as a therapeutic strategy in the treatment of devastating breathing disorders, such as during cervical spinal injury or motor neuron disease.

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Developmental Aspects of the Upper Airway: Report from an NHLBI Workshop, March 5-6, 2009

Cited by 26 publications

References 62 publications

Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells

Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells

Asthma: a simple concept but in reality a complex disease

Systemic inflammation impairs respiratory chemoreflexes and plasticity

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