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Human amniotic stem cells improve hepatic microvascular dysfunction and portal hypertension in cirrhotic rats
Author(s) -
Pietrosi Giada,
FernándezIglesias Anabel,
Pampalone Mariangela,
OrtegaRibera Martí,
Lozano Juan J.,
GarcíaCalderó Héctor,
AbadJordà Laia,
Conaldi Pier G.,
Parolini Ornella,
Vizzini Giovanni,
Luca Angelo,
Bosch Jaime,
GraciaSancho Jordi
Publication year - 2020
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.14610
Subject(s) - medicine , stem cell , cirrhosis , hepatic stellate cell , amniotic epithelial cells , portal hypertension , mesenchymal stem cell , amniotic stem cells , endothelial stem cell , stem cell therapy , progenitor cell , cell therapy , pathology , adult stem cell , in vitro , biology , microbiology and biotechnology , biochemistry
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 CCl 4 inhalation) were co‐cultured with hAMSCs, hAECs or vehicle for 24 hours, and their RNA profile was analysed. In vivo: CCl 4 ‐cirrhotic rats received 4x10 6 hAMSCs, 4x10 6 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.