Intravital Imaging of Hepatic Blood Biliary Barrier in Live Mice

Vats, Ravi; Kamiński, Tomasz W.; Pradhan‐Sundd, Tirthadipa

doi:10.1002/cpz1.256

Cited by 7 publications

(6 citation statements)

References 37 publications

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“…The method of qLIM is described elsewhere. 22 Texas red-dextran and AF488-P21 antibodies ( Online Supplementary Table S3 ) were administered intravascularly to visualize the blood flow in liver sinusoids and identify senescent cells in SCD (SS) and control (AS) mice, respectively ( Figure 1A , upper panel; Online Supplementary Movies S1 and S2 ). As shown in Figure 1A , P21-positive cells were localized close to the hepatic sinusoids resembling endothelial cell structures, suggestive of endothelial cell senescence.…”

Section: Resultsmentioning

confidence: 99%

Impaired hemoglobin clearance by sinusoidal endothelium promotes vaso-occlusion and liver injury in sickle cell disease

Kaminski,

Katoch,

et al. 2023

haematol

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Sickle cell disease (SCD) is a monogenic disorder that affects 100,000 African Americans and millions of people worldwide. Intra-erythrocytic polymerization of sickle hemoglobin (HbS) promotes erythrocyte sickling, impaired rheology, ischemia and hemolysis, leading to the development of progressive liver injury in SCD. Liver resident macrophages and monocytes are known to enable the clearance of HbS, however, the role of liver sinusoidal endothelial cells (LSECs) in HbS clearance and liver injury in SCD remains unknown. Using real-time intravital (in vivo) imaging in the mice liver as well as flow cytometric analysis and confocal imaging of primary human LSECs, we show for the first time that liver injury in SCD is associated with accumulation of HbS and iron in the LSECs, leading to LSEC senescence. Hb uptake by LSECs was mediated by micropinocytosis. Hepatic monocytes were observed to attenuate LSECsenescence by accelerating HbS clearance in the liver of SCD mice, however, this protection was impaired in P-selectin-deficient SCD mice secondary to reduced monocyte recruitment in the liver. These findings are the first to suggest that LSECs contribute to HbS clearance and HbS induced LSEC-senescence promotes progressive liver injury in SCD mice. Our results provide a novel insight into the pathogenesis of hemolysis induced chronic liver injury in SCD caused by LSEC senescence. Identifying the regulators of LSEC mediated HbS clearance may lead to new therapies to prevent the progression of liver injury in SCD.

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Section: Resultsmentioning

confidence: 99%

Impaired hemoglobin clearance by sinusoidal endothelium promotes vaso-occlusion and liver injury in sickle cell disease

Kaminski,

Katoch,

et al. 2023

haematol

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“…Intravital microscopy, which allows for the direct visualization of dynamic cellular processes in living subjects, has been useful in studying bile flow kinetics (157). Intravital microscopic study of cholestatic preclinical murine models revealed many of the cellular consequences of cholestasis discussed above, such as the loss of the blood-bile barrier integrity and impaired bile transporter function (158).…”

Section: Advanced Sequencing and Microscopymentioning

confidence: 99%

Pediatric Cholestatic Diseases: Common and Unique Pathogenic Mechanisms

Sutton,

Karpen,

Kamath

2024

Annu. Rev. Pathol. Mech. Dis.

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Cholestasis is the predominate feature of many pediatric hepatobiliary diseases. The physiologic flow of bile requires multiple complex processes working in concert. Bile acid (BA) synthesis and excretion, the formation and flow of bile, and the enterohepatic reuptake of BAs all function to maintain the circulation of BAs, a key molecule in lipid digestion, metabolic and cellular signaling, and, as discussed in the review, a crucial mediator in the pathogenesis of cholestasis. Disruption of one or several of these steps can result in the accumulation of toxic BAs in bile ducts and hepatocytes leading to inflammation, fibrosis, and, over time, biliary and hepatic cirrhosis. Biliary atresia, progressive familial intrahepatic cholestasis, primary sclerosing cholangitis, and Alagille syndrome are four of the most common pediatric cholestatic conditions. Through understanding the commonalities and differences in these diseases, the important cellular mechanistic underpinnings of cholestasis can be greater appreciated.

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“…It has been used to study the mechanism of glioblastoma cells in the tumor microenvironment, cellular interactions that contribute to biliary membrane integrity, and fast spatiotemporal cellular dynamics within neural networks. Additionally, it can be used to distinguish tumor-adjacent cancer cells tagged with fluorescent enzymes [6][7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

Stabilized two-photon intravital imaging using dexmedetomidine

Kim¹,

Cho²,

Paulson³

et al. 2023

Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XXI

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Two-photon microscopy provides subcellular-resolution imaging deep into animal tissues, and is frequently used for the study of biological and disease processes. However, its applicability in vivo is complicated by physiological movement. We demonstrate treatment with dexmedetomidine (DEX), an already FDA-approved alpha-2 adrenergic receptor agonist, to reduce tissue oscillation frequency and amplitude in the livers of anesthetized mice. Fluorescence intensity and focal quality fluctuations were found to improve for 30 minutes after administration, indicating that dexmedetomidine may be used to improve imaging quality in two-photon intravital microscopy studies. These results will likely generalize to other imaging modalities, target tissues, and animal models.

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Intravital Imaging of Hepatic Blood Biliary Barrier in Live Mice

Cited by 7 publications

References 37 publications

Impaired hemoglobin clearance by sinusoidal endothelium promotes vaso-occlusion and liver injury in sickle cell disease

Impaired hemoglobin clearance by sinusoidal endothelium promotes vaso-occlusion and liver injury in sickle cell disease

Pediatric Cholestatic Diseases: Common and Unique Pathogenic Mechanisms

Stabilized two-photon intravital imaging using dexmedetomidine

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