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

Pietrosi, Giada; Fernández-Iglesias, Anabel; Pampalone, Mariangela; Ortega-Ribera, Martí; Lozano, Juan J; García-Calderó, Héctor; Abad-Jordà, Laia; Conaldi, Pier G; Parolini, Ornella; Vizzini, Giovanni; Luca, Angelo; Bosch, Jaime; Gracia-Sancho, Jordi (2020). Human amniotic stem cells improve hepatic microvascular dysfunction and portal hypertension in cirrhotic rats. Liver international, 40(10), pp. 2500-2514. Blackwell Munksgaard 10.1111/liv.14610

[img] Text
liv.14610 (1).pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (2MB) | Request a copy

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

UniBE Contributor:

Bosch, Jaime and Gracia Sancho, Jorge Sergio

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1478-3223

Publisher:

Blackwell Munksgaard

Language:

English

Submitter:

Rahel Fuhrer

Date Deposited:

11 Dec 2020 11:40

Last Modified:

25 May 2021 17:02

Publisher DOI:

10.1111/liv.14610

PubMed ID:

32996708

Uncontrolled Keywords:

chronic liver disease hAEC hAMSC liver cirrhosis placenta portal hypertension

BORIS DOI:

10.7892/boris.148198

URI:

https://boris.unibe.ch/id/eprint/148198

Actions (login required)

Edit item Edit item
Provide Feedback