The influence of oxygen tension on the structure and function of isolated liver sinusoidal endothelial cells

Martínez, Iñigo; Nedredal, Geir I.; Øie, Cristina Ionica; Warren, Alessandra; Johansen, Oddmund; Couteur, David G. Le; Smedsrød, B

doi:10.1186/1476-5926-7-4

Cited by 58 publications

(66 citation statements)

References 25 publications

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“…In pancreatic IOL, the average PO2 measured in situ in anesthetized animals is 3540 Torr [134,135] . This level is slightly higher in healthy, wake animals and comparable to the PO2 values measured in the hepatic portal vein used for clinical islet transplantation [136] . However, following isolation and transplantation of IOL, this level changes dramatically.…”

Section: Oxygen Supplymentioning

confidence: 58%

Survival of encapsulated islets: More than a membrane story

Barkai¹,

Rotem²,

Vos³

2016

WJT

114

109

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Section: Oxygen Supplymentioning

confidence: 58%

Survival of encapsulated islets: More than a membrane story

Barkai¹,

Rotem²,

Vos³

2016

WJT

114

109

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“…One cannot translate these findings to MSCs, as both cancer cells [35] and hepatocytes [36] reside in highly oxygenated niches, while MSCs typically reside in niches with much lower physiological oxygen tensions [37]. Thus, the oxygen tensions capable of inducing necrosis may be different between cell types.…”

Section: Discussionmentioning

confidence: 99%

Measurement of oxygen tension within mesenchymal stem cell spheroids

Murphy

Hung

Browne-Bourne

et al. 2017

J. R. Soc. Interface.

111

120

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Spheroids formed of mesenchymal stem cells (MSCs) exhibit increased cell survival and trophic factor secretion compared with dissociated MSCs, making them therapeutically advantageous for cell therapy. Presently, there is no consensus for the mechanism of action. Many hypothesize that spheroid formation potentiates cell function by generating a hypoxic core within spheroids of sufficiently large diameters. The purpose of this study was to experimentally determine whether a hypoxic core is generated in MSC spheroids by measuring oxygen tension in aggregates of increasing diameter and correlating oxygen tension values with cell function. MSC spheroids were formed with 15 000, 30 000 or 60 000 cells per spheroid, resulting in radii of 176 + 8 mm, 251 + 12 mm and 353 + 18 mm, respectively. Oxygen tension values coupled with mathematical modelling revealed a gradient that varied less than 10% from the outer diameter within the largest spheroids. Despite the modest radial variance in oxygen tension, cellular metabolism from spheroids significantly decreased as the number of cells and resultant spheroid size increased. This may be due to adaptive reductions in matrix deposition and packing density with increases in spheroid diameter, enabling spheroids to avoid the formation of a hypoxic core. Overall, these data provide evidence that the enhanced function of MSC spheroids is not oxygen mediated.

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“…Since LSECs rapidly lose their in vivo uptake functions after isolation [50] endocytosis experiments were performed under serum-free conditions within 4 h of plating. Antibody markers for LSECs and Kupffer cells are listed in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

Efficient Uptake of Blood-Borne BK and JC Polyomavirus-Like Particles in Endothelial Cells of Liver Sinusoids and Renal Vasa Recta

et al. 2014

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Liver sinusoidal endothelial cells (LSECs) are specialized scavenger cells that mediate high-capacity clearance of soluble waste macromolecules and colloid material, including blood-borne adenovirus. To explore if LSECs function as a sink for other viruses in blood, we studied the fate of virus-like particles (VLPs) of two ubiquitous human DNA viruses, BK and JC polyomavirus, in mice. Like complete virions, VLPs specifically bind to receptors and enter cells, but unlike complete virions, they cannot replicate. 125I-labeled VLPs were used to assess blood decay, organ-, and hepatocellular distribution of ligand, and non-labeled VLPs to examine cellular uptake by immunohisto- and -cytochemistry. BK- and JC-VLPs rapidly distributed to liver, with lesser uptake in kidney and spleen. Liver uptake was predominantly in LSECs. Blood half-life (∼1 min), and tissue distribution of JC-VLPs and two JC-VLP-mutants (L55F and S269F) that lack sialic acid binding affinity, were similar, indicating involvement of non-sialic acid receptors in cellular uptake. Liver uptake was not mediated by scavenger receptors. In spleen, the VLPs localized to the red pulp marginal zone reticuloendothelium, and in kidney to the endothelial lining of vasa recta segments, and the transitional epithelium of renal pelvis. Most VLP-positive vessels in renal medulla did not express PV-1/Meca 32, suggesting location to the non-fenestrated part of vasa recta. The endothelial cells of these vessels also efficiently endocytosed a scavenger receptor ligand, formaldehyde-denatured albumin, suggesting high endocytic activity compared to other renal endothelia. We conclude that LSECs very effectively cleared a large fraction of blood-borne BK- and JC-VLPs, indicating a central role of these cells in early removal of polyomavirus from the circulation. In addition, we report the novel finding that a subpopulation of endothelial cells in kidney, the main organ of polyomavirus persistence, showed selective and rapid uptake of VLPs, suggesting a role in viremic organ tropism.

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The influence of oxygen tension on the structure and function of isolated liver sinusoidal endothelial cells

Cited by 58 publications

References 25 publications

Survival of encapsulated islets: More than a membrane story

Survival of encapsulated islets: More than a membrane story

Measurement of oxygen tension within mesenchymal stem cell spheroids

Efficient Uptake of Blood-Borne BK and JC Polyomavirus-Like Particles in Endothelial Cells of Liver Sinusoids and Renal Vasa Recta

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