Pro-fibrotic biomarkers in ex vivo lung tissue slices: A species comparison

2017 ◽  
Author(s):  
Christina Hesse ◽  
Samuel Mang ◽  
Heinz-Gerd Hoymann ◽  
Monika Niehof ◽  
Peter Braubach ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Ex Vivo ◽  
Species Comparison ◽  
Tissue Slices

scholarly journals Ex vivo infection of murine precision-cut lung tissue slices with Mycobacterium abscessus: a model to study antimycobacterial agents

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Carmen Amelia Molina-Torres ◽  
Oscar Noé Flores-Castillo ◽  
Irma Edith Carranza-Torres ◽  
Nancy Elena Guzmán-Delgado ◽  
Ezequiel Viveros-Valdez ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Time Course ◽  
Ex Vivo ◽  
Virulent Strain ◽  
Mycobacterium Abscessus ◽  
New Drugs ◽  
Histopathological Analysis ◽  
Ex Vivo Model ◽  
Tissue Slices ◽  
Precision Cut Lung Slices

Abstract Background Multidrug-resistant infections due to Mycobacterium abscessus often require complex and prolonged regimens for treatment. Here, we report the evaluation of a new ex vivo antimicrobial susceptibility testing model using organotypic cultures of murine precision-cut lung slices, an experimental model in which metabolic activity, and all the usual cell types of the organ are found while the tissue architecture and the interactions between the different cells are maintained. Methods Precision cut lung slices (PCLS) were prepared from the lungs of wild type BALB/c mice using the Krumdieck® tissue slicer. Lung tissue slices were ex vivo infected with the virulent M. abscessus strain L948. Then, we tested the antimicrobial activity of two drugs: imipenem (4, 16 and 64 μg/mL) and tigecycline (0.25, 1 and 4 μg/mL), at 12, 24 and 48 h. Afterwards, CFUs were determined plating on blood agar to measure the surviving intracellular bacteria. The viability of PCLS was assessed by Alamar Blue assay and corroborated using histopathological analysis. Results PCLS were successfully infected with a virulent strain of M. abscessus as demonstrated by CFUs and detailed histopathological analysis. The time-course infection, including tissue damage, parallels in vivo findings reported in genetically modified murine models for M. abscessus infection. Tigecycline showed a bactericidal effect at 48 h that achieved a reduction of > 4log10 CFU/mL against the intracellular mycobacteria, while imipenem showed a bacteriostatic effect. Conclusions The use of this new organotypic ex vivo model provides the opportunity to test new drugs against M. abscessus, decreasing the use of costly and tedious animal models.

Pseudomonas aeruginosa flagellin modulates the immune response in ex vivo lung tissue slices

2019 ◽  
Author(s):  
Valerie Beneke ◽  
Nora Grahl ◽  
Olga Danov ◽  
Sebastian Konzok ◽  
Peter Braubach ◽  
...  
Keyword(s):  
Immune Response ◽  
Pseudomonas Aeruginosa ◽  
Lung Tissue ◽  
Ex Vivo ◽  
Tissue Slices

Unravelling specific mechanisms of wound healing and pulmonary fibrosis in human ex vivo lung tissue slices

2018 ◽  
Author(s):  
Christina Hesse ◽  
Samuel Mang ◽  
Stefan-Lutz Wollin ◽  
Monika Niehof ◽  
Peter Braubach ◽  
...  
Keyword(s):  
Wound Healing ◽  
Pulmonary Fibrosis ◽  
Lung Tissue ◽  
Ex Vivo ◽  
Tissue Slices

scholarly journals Spatially resolved microfluidic stimulation of lymphoid tissue ex vivo

The Analyst ◽  
2017 ◽  
Vol 142 (4) ◽  
pp. 649-659 ◽  
Author(s):  
Ashley E. Ross ◽  
Maura C. Belanger ◽  
Jacob F. Woodroof ◽  
Rebecca R. Pompano
Keyword(s):  
Lymph Node ◽  
Targeted Delivery ◽  
Lymphoid Tissue ◽  
Ex Vivo ◽  
Tissue Slices ◽  
Microfluidic Platform ◽  
Spatially Resolved ◽  
Local Stimulation ◽  
Stimulation Of

We present the first microfluidic platform for local stimulation of lymph node tissue slices and demonstrate targeted delivery of a model therapeutic.

Surfactant metabolism in surfactant protein A-deficient mice

1997 ◽  
Vol 272 (3) ◽  
pp. L479-L485 ◽  
Author(s):  
M. Ikegami ◽  
T. R. Korfhagen ◽  
M. D. Bruno ◽  
J. A. Whitsett ◽  
A. H. Jobe
Keyword(s):  
Lung Tissue ◽  
Protein A ◽  
Surfactant Protein ◽  
Normal Lung ◽  
Tissue Slices ◽  
Normal Lung Function ◽  
Deficient Mice ◽  
Surfactant Metabolism

In the present study we asked if surfactant metabolism was altered in surfactant protein (SP) A-deficient mice in vivo. Although previous studies in vitro demonstrated that SP-A modulates surfactant secretion and reuptake by type II cells, mice made SP-A deficient by homologous recombination grow and reproduce normally and have normal lung function. Alveolar and lung tissue saturated phophatidylcholine (Sat PC) pools were 50 and 26% larger, respectively, in SP-A(-/-) mice than in SP-A(+/+) mice. Radiolabeled choline and palmitate incorporation into lung Sat PC was similar both in vivo and for lung tissue slices in vitro from SP-A(+/+) and SP-A(-/-) mice. Percent secretion of radiolabeled Sat PC was unchanged from 3 to 15 h, although SP-A(-/-) mice retained more labeled Sat PC in the alveolar lavages at 48 h (consistent with the increased surfactant pool sizes). Clearance of radiolabeled dipalmitoylphosphatidylcholine and SP-B from the air spaces after intratracheal injection was similar in SP-A(-/-) and SP-A(+/+) mice. Lack of SP-A had minimal effects on the overall metabolism of Sat PC or SP-B in mice.

Chronic strain alters the passive and contractile properties of rabbit airways

2005 ◽  
Vol 98 (5) ◽  
pp. 1949-1954 ◽  
Author(s):  
R. S. Tepper ◽  
R. Ramchandani ◽  
E. Argay ◽  
L. Zhang ◽  
Z. Xue ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Mechanical Strain ◽  
Contractile Properties ◽  
Tissue Slices ◽  
Strain Effects ◽  
Peripheral Airways ◽  
Airway Lumen ◽  
Physiological Properties ◽  
Passive Compliance ◽  
Balance Of Forces

Pathophysiological conditions of the lung may shift the balance of forces so as to chronically alter the amount of strain imposed on the airways. This chronic strain could result in changes in the structure and/or function of the airways that affect its physiological properties. We evaluated the effects of imposing physiological levels of chronic mechanical strain on the passive and active physiological properties of intraparenchymal rabbit airways. Isolated bronchial segments were cultured for 48 h at transmural pressures of 0 cmH2O (No Strain) or 7 cmH2O (Strain). Effects of strain on small parenchymal airways were evaluated in lung tissue slices cultured under conditions of No Strain or ∼50% increased in diameter (Strain). Chronic strain resulted in a higher passive compliance of the bronchial segments and larger airway lumen size. In addition, bronchi not subjected to chronic Strain were more responsive to ACh than bronchi subjected to chronic Strain, and airways in lung slices subjected to No Strain narrowed more in response to ACh than airways in lung slices subjected to Strain. The greatest effects of chronic strain occurred in the smallest sized airways. Our results suggest that chronic distension of the airways has physiologically important effects on their passive and active properties, which are most prominent in the smaller, more peripheral airways.

scholarly journals Gene transfer to adult human lung tissue ex vivo

Gene Therapy ◽  
2000 ◽  
Vol 7 (8) ◽  
pp. 675-678 ◽  
Author(s):  
S McBride ◽  
D Rannie ◽  
D J Harrison
Keyword(s):  
Gene Transfer ◽  
Lung Tissue ◽  
Human Lung ◽  
Ex Vivo ◽  
Human Lung Tissue ◽  
Adult Human ◽  
Adult Human Lung

scholarly journals TMOD-31. ADAPTING ENGINEERED CELL THERAPIES TO UNDERSTAND AND OVERCOME GLIOBLASTOMA RESISTANCE USING INTEGRATED IN VIVO AND EX VIVO MODELS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi269-vi269
Author(s):  
Andrew Satterlee ◽  
Denise Dunn ◽  
Scott Floyd ◽  
Shawn Hingtgen
Keyword(s):  
Primary Tumor ◽  
Ex Vivo ◽  
Tumor Burden ◽  
In Vivo Studies ◽  
Pcr Analysis ◽  
Tissue Slices ◽  
Live Animal ◽  
Invasive Tumor ◽  
Recurrent Tumors

Abstract Genetically engineered neural stem cells (NSCs) are a promising therapy for the highly aggressive brain cancer glioblastoma (GBM), yet treatment durability remains a major challenge. We sought to define the events that contribute to dynamic adaption of GBM during NSC treatment and develop strategies to convert initial tumor kill into sustained GBM suppression. Using a unique hybrid tumor model treated with human skin-derived induced NSCs (iNSCs) releasing the pro-apoptotic agent TRAIL, we investigated how spatial distribution of tumor and iNSCs affects GBM adaption throughout recurrence. Serial bioluminescent imaging (BLI) was used to track tumor volumes in vivo, while a subset of mice were sacrificed 6, 13, and 20 days post-treatment to harvest brains and generate living ex vivo tissue slices. Live animal imaging showed iNSC-TRAIL treatment rapidly decreased tumor volumes when delivered into the primary tumor mass; however, minimal impact on tumor growth was observed when cells were delivered into distal regions of the brain. In contrast, high-resolution imaging of living brain sections showed extensive impacts of iNSC-TRAIL therapy that could not be visualized with BLI. The living slices showed iNSC-TRAIL treatment into the primary tumor decreased the solid, but not the invasive, tumor burden. Treatment into the lateral ventricles did impact tumor kill and was more effective at treating the invasive tumor burden and maintaining inhibition than treatment into the contralateral parenchyma. We next utilized the living tissue slices to explore the sensitivity of the recurrent tumors to TRAIL. When therapy was applied to slices harboring recurrent tumor, treatment again significantly reduced tumor volumes, suggesting that tumors had not acquired TRAIL resistance. These results informed an additional in vivo survival study and subsequent PCR analysis of untreated and recurrent tumors, and combine the fidelity of in vivo studies with the speed and spatial resolution of living brain slice technology.

Sign in / Sign up

Export Citation Format

Share Document