Z Gastroenterol 2018; 56(08): e248
DOI: 10.1055/s-0038-1668780
Kurzvorträge
Leber und Galle
Leber: Fibrose, Steatose, Speicherkrankheiten – Donnerstag, 13. September 2018, 09:50 – 11:18, 22a
Georg Thieme Verlag KG Stuttgart · New York

Systemic treatment with adipose-tissue derived mesenchymal cells (MSC) induce regression of fibrosis and improves hepatic arterial vascular dysfunction and angiogenesis

A Gluhmann
1   Martin-Luther-Universität Halle, Klinik für Innere Medizin I, Halle/Saale, Deutschland
,
S Pohl
1   Martin-Luther-Universität Halle, Klinik für Innere Medizin I, Halle/Saale, Deutschland
,
A Zipprich
1   Martin-Luther-Universität Halle, Klinik für Innere Medizin I, Halle/Saale, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
13 August 2018 (online)

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We have shown that MSCs improved portal pressure and fibrosis in cirrhotic livers. The liver has a dual blood supply and in cirrhosis the hepatic artery shows vascular dysfunction and increased angiogenesis. So far, it is unknown what role the hepatic artery has under regression of fibrosis. The aim of the study was to investigate the hepatic arterial vascular changes under regression of fibrosis in MSC treated cirrhotic animals.

Methods:

Systemic treatment with adipose tissue-derived MSCs, pre-differentiated into hepatocytic cells, was investigated in CCl4-cirrhosis with ascites. Cirrhotic animals without treatment served as controls. Three weeks after treatment with MSC a bivascular liver perfusion was performed in presence or absence of NO-blocker LNMMA and log EC50 of increasing doses of methoxamine (vasoconstrictor) was calculated. Additional animals were sacrificed to extract sinusoidal endothelial cells (LSEC) and liver samples for investigation of cellular mechanisms.

Results:

Log EC50 of hepatic artery in absence of LNMMA was not different between control animals and MSC treated animals. Presence of LNMMA increased the logEC50 significant in MSC treated animals compared to control animals (p = 0.008). TGFbeta (p = 0.01) and alphaSMA (p = 0.01) were significant lower in livers of treated compared to control animals. LSEC of MSC treated animals revealed significant lower VEGF levels (p = 0.007) compared to control animals. Endothelial NOS and phospho eNOS were unchanged between both groups.

Conclusion:

Treatment of cirrhotic livers with MSC increase the sensitivity to vasoconstrictor of the hepatic artery implicating less vascular dysfunction. Levels of VEGF were decreased in MSC treated animals suggesting less angiogenesis. Therefore, improvement of hepatic arterial dysfunction and angiogenesis seems to be important in MSC induced regression of fibrosis.