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RESEARCH PRODUCT
Human amniotic stem cells improve hepatic microvascular dysfunction and portal hypertension in cirrhotic rats
Angelo LucaOrnella ParoliniOrnella ParoliniJordi Gracia-sanchoJuan José LozanoJaime BoschPier G. ConaldiLaia Abad-jordàGiada PietrosiMariangela PampaloneAnabel Fernández-iglesiasGiovanni VizziniHéctor García-calderóMartí Ortega-riberasubject
Liver CirrhosisPathologymedicine.medical_specialtyhAECCirrhosisplacentaPortal venous pressure03 medical and health sciences0302 clinical medicineHypertension PortalSettore BIO/13 - BIOLOGIA APPLICATAAnimalsHumansMedicineAmnion610 Medicine & healthHepatologymedicine.diagnostic_testbusiness.industryMicrocirculationStem Cellschronic liver diseaseportal hypertensionEndothelial CellsAmniotic stem cellsmedicine.diseaseRatsLiver030220 oncology & carcinogenesisHepatic stellate cellPortal hypertensionVascular Resistance030211 gastroenterology & hepatologyStem cellbusinessHepatic fibrosisLiver function testshAMSCdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-01-01 | Liver International |