Tissue Specific Vasculature and Model Systems Flashcards
Q1: Why do organs require tissue-specific vasculature? Provide at least two examples.
A: Different organs perform unique functions that demand specialized vascular structures:
Kidneys filter large volumes of blood, requiring fenestrated endothelium for selective permeability.
Blood-brain barrier (BBB) has continuous, non-fenestrated endothelium with tight junctions to prevent neurotoxic substances from entering the CNS.
Q2: Compare the three types of endothelial cell structures and their functional significance.
A:
Continuous, non-fenestrated: Tight junctions, low permeability (e.g., brain, heart). Maintains strict barrier.
Fenestrated: Moderate permeability due to pores (e.g., kidneys). Allows filtration of small molecules.
Discontinuous (sinusoidal): High permeability, large gaps (e.g., liver, spleen). Facilitates movement of cells and large proteins.
Q3: Describe the role of Piezo1 in lung endothelial function and its clinical significance.
A: Piezo1 is a mechanosensitive ion channel in lung endothelial cells. It regulates VE-cadherin stability and barrier function. Loss of Piezo1 leads to degradation of VE-cadherin, increased vascular permeability, and conditions like pulmonary edema.
Q4: Outline the inflammatory response in the alveolus following injury or infection.
A:
Stimulus (e.g., virus, bacteria) in alveolus triggers cytokine release.
Upregulation of adhesion molecules (e.g., ICAM-1, selectins) on endothelium.
Neutrophils adhere, roll, and transmigrate into alveolar space.
They degranulate, release ROS, and undergo NETosis.
This leads to tissue damage and can cause ARDS.
Q5: What are organs-on-chips and how do they improve on traditional in vitro models?
A: OOCs are microfluidic devices that mimic organ-level function using cultured cells and dynamic flow. Unlike static cultures (flasks, wells), OOCs:
Replicate mechanical forces (e.g., stretch, shear)
Allow multi-cell type interactions
Enable live imaging and drug testing in near-physiological conditions
Q6: How did the lung-on-a-chip model demonstrate infection and immune response?
A:
TNF-α applied to the epithelial side increased ICAM-1 on the endothelium.
Neutrophils flowed through the endothelial channel adhered and transmigrated to epithelial side.
E. coli infection further triggered neutrophil activity, simulating immune response to pathogens.
Q7: What were the outcomes of simulating asthma and COPD in lung-on-chip models?
A:
Asthma simulation (IL-13): Increased goblet cells, higher cytokine secretion, reduced cilia beating.
COPD simulation (LPS): Increased IL-8 and M-CSF, enhanced neutrophil adhesion.
Drug testing: BRD4 inhibitor reduced neutrophil adhesion, while Budesonide had little effect, mimicking clinical outcomes better than static models.
Q8: Discuss the advantages and limitations of microfluidics and OOCs.
A:
Advantages:
Mimic specific physiological features
Control of shear and mechanical forces
Live cell imaging
Potential to reduce animal testing
Limitations:
Difficult to culture multiple cell types
Lack systemic complexity (e.g., turbulence)
Fabrication can be complex and costly
