Coming to terms with tissue engineering and regenerative medicine in the lung

Prakash, Y. S.; Tschumperlin, Daniel J.; Stenmark, Kurt R.

doi:10.1152/ajplung.00204.2015

Cited by 36 publications

(36 citation statements)

References 229 publications

(249 reference statements)

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“…Sorting and seeding of mesenchymal cell subpopulations that support vascularization in organoids may be one means by which to enhance organoid growth and engraftment potential. Finally, inclusion of additional matrix and soluble cues [13] will likely be essential to further optimize cell organization, growth and differentiation, and in vivo integration of airway organoid grafts with host tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Current approaches to engraft dissociated cells in the lung show promise, but have thus far been limited to the setting of severe infections [8] or radiation-induced preconditioning [9]. A major alternative emphasis has been on the generation of decellularized and recellularized lung scaffolds as an engineered organ replacement [10–13]. Relatively less attention has been devoted to the de novo generation of complex three-dimensional lung-like tissues in culture suitable for eventual translational applications.…”

Section: Introductionmentioning

confidence: 99%

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Human airway organoid engineering as a step toward lung regeneration and disease modeling

et al. 2017

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human airway organoid engineering as a step toward lung regeneration and disease modeling

et al. 2017

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“…It is currently well recognized that stem cells multi-potency is modulated by signals of the surrounding local microenvironment, including biophysical and biochemical cues presented by the matrix and soluble mediators secreted by neighbor cells or coming from systemic pathways [12, 21]. In fact, as different organs/tissues are subjected to particular biophysical stimuli during normal function, it is reasonable to expect that physiological conditions could promote stem cell differentiation towards specific phenotypes in vitro.…”

Section: Reviewmentioning

confidence: 99%

“…The differentiating effects of cyclic stretch depend, however, on whether the protocol is conducted in 2-D or 3-D microenvironments [46]. Spontaneous breathing cycles, causing rhythmic inflation/deflation of lungs, exert mechanical forces which provide cues that modulate cell growth, survival and direct stem cells fate [21]. Moreover, distinct mechanical environments such as compressive and tensile strain provoke different structural distortions and change cell volumes, in a way that influence gene expression and morphology [30, 47].…”

Section: Reviewmentioning

confidence: 99%

“…It is known that this mechanical stimulus modulates endothelial function and, potentially, endothelial specification of stem cells [21, 52]. Wang et al [53] demonstrated that laminar shear stress promotes endothelial cell fate in a murine mesenchymal progenitor cell line: cells aligned in the direction of flow, upregulated endothelial cell markers and formed capillary-like tube structures.…”

Section: Reviewmentioning

confidence: 99%

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Lung bioengineering: physical stimuli and stem/progenitor cell biology interplay towards biofabricating a functional organ

et al. 2016

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A current approach to obtain bioengineered lungs as a future alternative for transplantation is based on seeding stem cells on decellularized lung scaffolds. A fundamental question to be solved in this approach is how to drive stem cell differentiation onto the different lung cell phenotypes. Whereas the use of soluble factors as agents to modulate the fate of stem cells was established from an early stage of the research with this type of cells, it took longer to recognize that the physical microenvironment locally sensed by stem cells (e.g. substrate stiffness, 3D architecture, cyclic stretch, shear stress, air-liquid interface, oxygenation gradient) also contributes to their differentiation. The potential role played by physical stimuli would be particularly relevant in lung bioengineering since cells within the organ are physiologically subjected to two main stimuli required to facilitate efficient gas exchange: air ventilation and blood perfusion across the organ. The present review focuses on describing how the cell mechanical microenvironment can modulate stem cell differentiation and how these stimuli could be incorporated into lung bioreactors for optimizing organ bioengineering.

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Advanced In Vitro Lung Models for Drug and Toxicity Screening: The Promising Role of Induced Pluripotent Stem Cells

Moreira¹,

Müller

Costa³

et al. 2021

Advanced Biology

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Respiratory diseases are among the global leading causes of morbidity and mortality. Acute conditions arising from infection, such as pneumonia and tuberculosis, affect millions of people worldwide, the latter being the most common lethal infectious disease with 1.4 million annual deaths. [1] Upon infection, the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which caused a worldwide pandemic, leads to the clinical picture of the coronavirus disease-2019 (COVID-19) with possibly severe and life-threatening progression. Lung cancer is the most frequently diagnosed malignancy and the main cause of cancer-related death, [2] with markedly low survival rates especially when the diagnosis is performed at an advanced state of the disease. [3] Moreover, chronic respiratory diseases (CRDs), including chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung disease (ILD), have consistently received less attention in comparison to other non-communicable diseases, continuing to exert a considerable socioeconomic impact. [4,5] Risk factors for the development of respiratory diseases include, for example, tobacco use and second-hand smoke, as well as exposure to air-pollutants, which has been accentuated with the widespread use of fossil fuels. [4] It is clear that a great number of these risks can be mitigated by lifestyle changes, promoted by anti-tobacco campaigns already in place at a global scale and by the use of renewable, clean energy sources, and two recent studies indicate that the age-standardized incidence and prevalence of CRDs has decreased from 1990 to 2017. [4,5] However, the risk of developing CRDs, particularly COPD, appears to increase steeply with age; [4,5] most strikingly, these diseases were the third leading cause of death in 2017 [4] and potentially in 2020. [6] In addition to microbial, environmental, and lifestyle-related factors, a large number of lung diseases have a genetic origin. [7] Cystic fibrosis (CF), for example, is an incurable hereditary disorder known to originate from different mutations in the gene coding for the CF transmembrane conductance regulator (CFTR), an ion transporter, resulting in severe alterations in pulmonary physiology that culminate in impaired lung function, respiratory distress and, ultimately, death. [8,9]

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Coming to terms with tissue engineering and regenerative medicine in the lung

Abstract: Prakash YS, Tschumperlin DJ, Stenmark KR. Coming to terms with tissue engineering and regenerative medicine in the lung.

Cited by 36 publications

References 229 publications

Human airway organoid engineering as a step toward lung regeneration and disease modeling

Human airway organoid engineering as a step toward lung regeneration and disease modeling

Lung bioengineering: physical stimuli and stem/progenitor cell biology interplay towards biofabricating a functional organ

Advanced In Vitro Lung Models for Drug and Toxicity Screening: The Promising Role of Induced Pluripotent Stem Cells

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