Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Oct;40(10):2500-2514.
doi: 10.1111/liv.14610. Epub 2020 Aug 9.

Human amniotic stem cells improve hepatic microvascular dysfunction and portal hypertension in cirrhotic rats

Giada Pietrosi  1 , Anabel Fernández-Iglesias  2 , Mariangela Pampalone  3 , Martí Ortega-Ribera  2 , Juan J Lozano  2 , Héctor García-Calderó  2 , Laia Abad-Jordà  2 , Pier G Conaldi  1 , Ornella Parolini  4   5 , Giovanni Vizzini  1 , Angelo Luca  1 , Jaime Bosch  2   6 , Jordi Gracia-Sancho  2   6
Affiliations

Human amniotic stem cells improve hepatic microvascular dysfunction and portal hypertension in cirrhotic rats

Giada Pietrosi et al. Liver Int. 2020 Oct.

Abstract

Background and aims: Portal hypertension is the main consequence of cirrhosis, responsible for the complications defining clinical decompensation. The only cure for decompensated cirrhosis is liver transplantation, but it is a limited resource and opens the possibility of regenerative therapy. We investigated the potential of primary human amniotic membrane-derived mesenchymal stromal (hAMSCs) and epithelial (hAECs) stem cells for the treatment of portal hypertension and decompensated cirrhosis.

Methods: In vitro: Primary liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs) from cirrhotic rats (chronic CCl4 inhalation) were co-cultured with hAMSCs, hAECs or vehicle for 24 hours, and their RNA profile was analysed. In vivo: CCl4-cirrhotic rats received 4x106 hAMSCs, 4x106 hAECs, or vehicle (NaCl 0.9%) (intraperitoneal). At 2-weeks we analysed: a) portal pressure (PP) and hepatic microvascular function; b) LSECs and HSCs phenotype; c) hepatic fibrosis and inflammation.

Results: In vitro experiments revealed sinusoidal cell phenotype amelioration when co-cultured with stem cells. Cirrhotic rats receiving stem cells, particularly hAMSCs, had significantly lower PP than vehicle-treated animals, together with improved liver microcirculatory function. This hemodynamic amelioration was associated with improvement in LSECs capillarization and HSCs de-activation, though hepatic collagen was not reduced. Rats that received amnion derived stem cells had markedly reduced hepatic inflammation and oxidative stress. Finally, liver function tests significantly improved in rats receiving hAMSCs.

Conclusions: This preclinical study shows that infusion of human amniotic stem cells effectively decreases PP by ameliorating liver microcirculation, suggesting that it may represent a new treatment option for advanced cirrhosis with portal hypertension.

Keywords: chronic liver disease; hAEC; hAMSC; liver cirrhosis; placenta; portal hypertension.

PubMed Disclaimer

References

REFERENCES

    1. Gracia-Sancho J, Laleman W. Mechanisms of portal hypertension: Bench to bedside. Clin Liver Dis. 2016;8:160-166.
    1. D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies. J Hepatol. 2006;44:217-231.
    1. Garcia-tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal Hypertensive Bleeding in Cirrhosis : Risk Stratification, Diagnosis, and Management : 2016 Practice Guidance by the American Association for the Study of Liver Diseases A. Purpose and Scope. Hepatology. 2017;65:310-335.
    1. Guixé-Muntet S, Zhu C-P, Xie W-F, Gracia-Sancho J. Novel therapeutics for portal hypertension and fibrosis in chronic liver disease. Pharmacol Ther. 2020;215:107626. https://doi.org/10.1016/j.pharmthera.2020.107626
    1. Marcellin P, Kutala BK. Liver diseases: A major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int. 2018;38:2-6.

Publication types

LinkOut - more resources