The Preparation of Decellularized Mouse Lung Matrix Scaffolds for Analysis of Lung Regenerative Cell Potential

Bölükbas, Deniz A.; Santis, Martina M. De; Alsafadi, Hani N.; Doryab, Ali; Wagner, Darcy E.

doi:10.1007/978-1-4939-9086-3_20

Cited by 12 publications

(8 citation statements)

References 44 publications

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“…We explanted tumorous lungs from healthy or Kras LA2 mutant mice and introduced actively or passively targeting MSNs for 3 h at controlled flow rates using an ex vivo system containing ventilation and perfusion which we have previously described ( Figure 6A). [26] Our first data using organ-restricted vascular delivery (ORVD) indicated that nanoparticles were homogeneously distributed in healthy mouse lungs and located with close proximity to endothelial cells (CD31 positive), suggesting their retention inside healthy blood vessels ( Figure S8A). On the other hand, we observed enhanced delivery of MSNAVI, MSNtEGFR, and MSNtCCR2 into the cores of solid lung tumors in a reproducible manner, regardless of their surface functionalization for active targeting ( Figure 6B).…”

Section: Organ-restricted Vascular Delivery Of Msns Enables Specific mentioning

confidence: 95%

“…Organ-restricted vascular delivery: Heart-lung blocks from WT and Kras LA2 mutant mice were extracted and placed into the ex vivo perfusion/ventilation system as described by Bölükbas et al [26] and schematically depicted in Fig 5A. The system was protected from light for all of the experiments containing the fluorescent MSNs. The ex vivo heart-lung blocks were submerged in cell culture media supplemented with 10% FCS and 1% Pen/Strep in the internal incubation chamber kept at 37°C and were mechanically ventilated with a respiratory frequency of 100 strokes/minute and 100 μL stroke volume throughout the 3 h nanoparticle exposure.…”

Section: In Vivo Biodistribution Studiesmentioning

confidence: 99%

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Organ-restricted vascular delivery of nanoparticles for lung cancer therapy

Bölükbas

Datz

Meyer‐Schwickerath

et al. 2020

Preprint

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AbstractNanomedicines hold immense promise for a number of devastating diseases due to the ability to custom-design both the carrier and cargo. However, their clinical implementation has been hampered by physicochemical and biological barriers and off-target deposition which impair cell specific targeting, especially in internal organs. This study reports a new delivery approach using organ-restricted vascular delivery to allow for direct administration and recirculation of stimuli-responsive nanoparticles to promote cellular uptake into an organ of interest. Using this technique, nanoparticles reach the interior of dense tumors and are selectively taken up by lung cancer cells. Importantly, this surgical approach is essential as the same nanoparticles do not reach lung tumor cells upon systemic or intratracheal administration. Organ-restricted vascular delivery thus opens up new avenues for optimized nanotherapies for cancer and other diseases.

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Section: Organ-restricted Vascular Delivery Of Msns Enables Specific mentioning

confidence: 95%

Section: In Vivo Biodistribution Studiesmentioning

confidence: 99%

Organ-restricted vascular delivery of nanoparticles for lung cancer therapy

Bölükbas

Datz

Meyer‐Schwickerath

et al. 2020

Preprint

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“…The use of lung explants to study development-relevant processes continues to be refined (248,505,644), although these approaches are generally applied to the study of early lung development, and not alveolarization. For the first time, precision-cut lung slices (16) have been used to visualize dynamic epithelial cells behavior during alveologenesis (7), and progress continues to be made in the generation and application of decellularized lung and scaffolds to study lung regeneration, and processes relevant to lung development (50,591).…”

Section: In Vitro Approachesmentioning

confidence: 99%

Recent advances in our understanding of the mechanisms of lung alveolarization and bronchopulmonary dysplasia

Lignelli

Palumbo

Myti

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

107

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Bronchopulmonary dysplasia (BPD) is the most common cause of morbidity and mortality in preterm infants. A key histopathological feature of BPD is stunted late lung development, where the process of alveolarization—the generation of alveolar gas exchange units—is impeded, through mechanisms that remain largely unclear. As such, there is interest in the clarification both of the pathomechanisms at play in affected lungs, and the mechanisms of de novo alveoli generation in healthy, developing lungs. A better understanding of normal and pathological alveolarization might reveal opportunities for improved medical management of affected infants. Furthermore, disturbances to the alveolar architecture are a key histopathological feature of several adult chronic lung diseases, including emphysema and fibrosis, and it is envisaged that knowledge about the mechanisms of alveologenesis might facilitate regeneration of healthy lung parenchyma in affected patients. To this end, recent efforts have interrogated clinical data, developed new—and refined existing—in vivo and in vitro models of BPD, have applied new microscopic and radiographic approaches, and have developed advanced cell-culture approaches, including organoid generation. Advances have also been made in the development of other methodologies, including single-cell analysis, metabolomics, lipidomics, and proteomics, as well as the generation and use of complex mouse genetics tools. The objective of this review is to present advances made in our understanding of the mechanisms of lung alveolarization and BPD over the period 1 January 2017–30 June 2019, a period that spans the 50th anniversary of the original clinical description of BPD in preterm infants.

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“…Another possibility is that the utility of PDA for binding MnPNH 2 to the scaffold would be seen only at much lower concentrations of MnPNH 2 (less than the min imum concentration of 0.4 mM tested), where increased re tention aided by an adhesive would rise above saturation and The decellularized bladder, tracheal, and lung models used to exemplify our proposed labeling and monitoring approach were chosen because of their immediacy and rel evance in the field of tissue engineering. Research centers around the world are investigating ways using dECM mate rials to regenerate the bladder, 30 trachea, 7,31 and lungs, 32,33 amongst the many other tissue types not covered in this study. Because these efforts are largely in the infant stages of devel opment, where optimal cell types, for example, have yet to be uncovered, the application of our labeling method to study regeneration in vivo would yield the greatest insight when the regeneration approach itself has matured further to a stage where new tissue growth is confirmed but how to optimize that growth needs to be answered.…”

Section: F I G U R Ementioning

confidence: 99%

MRI method for labeling and imaging decellularized extracellular matrix scaffolds for tissue engineering

Szulc

Ahmadipour

Aoki

et al. 2019

Magnetic Resonance in Med

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Purpose To develop a facile method for labeling and imaging decellularized extracellular matrix (dECM) scaffolds intended for regenerating 3D tissues. Methods A small molecule manganese porphyrin, MnPNH2, was synthesized and used to label dECM scaffolds made from porcine bladder and trachea and murine whole lungs. The labeling protocol was optimized on bladder dECM, and imaging on a 3T clinical scanner was performed to assess reductions in T1 and T2 relaxation times. In vivo MRI was performed on dECM injected in the rat dorsum to verify sensitivity of detection. Toxicity assays for cell viability, metabolism, and proliferation were performed on human umbilical vein endothelial cells. The incorporation of MnPNH2 and its long‐term retention in dECM were assessed on transmission electron microscopy and ultraviolet absorbance of eluted MnPNH2 over time. Results All tissues, including thick whole 3D organs, were uniformly labeled and demonstrated high signal‐to‐noise on MRI. A nearly 10‐fold reduction in T1 was consistently obtained at a labeling dose of 0.4 mM, and even 0.2 mM provided sufficient contrast in vivo and ex vivo. No toxicity was observed up to 0.4 mM, the maximum tested. Binding studies suggested nonspecific association, and retention studies in the labeled whole decellularized lungs revealed less than 20% MnPNH2 loss over 30 days, the majority occurring in the first 3 days after labeling. Conclusion The proposed labeling method is the first report for visualizing dECM on MRI and has the potential for long‐term monitoring and optimization of dECM‐based organ tissue engineering.

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The Preparation of Decellularized Mouse Lung Matrix Scaffolds for Analysis of Lung Regenerative Cell Potential

Cited by 12 publications

References 44 publications

Organ-restricted vascular delivery of nanoparticles for lung cancer therapy

Organ-restricted vascular delivery of nanoparticles for lung cancer therapy

Recent advances in our understanding of the mechanisms of lung alveolarization and bronchopulmonary dysplasia

MRI method for labeling and imaging decellularized extracellular matrix scaffolds for tissue engineering

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