Introduction: Available therapies for hepatocellular carcinoma (HCC) have a modest impact on patient survival, making it necessary to develop new treatments. SMYD2 is a methyltransferase that acts as an oncogene in numerous types of cancers. The aim of ou

DOMÍNGUEZ, LUCIANA; MILAGROS ALBORNOZ; JUAN BAYO; CANTERO, MARIA JOSE; BARBARA BUELONI; CATALINA ATORRASAGASTI; CELESTE BIANI; CARLOS LUZZANI; MARIANA GARCIA; GUSTAVO YANNARELLI; ESTEBAN FIORE; GUILLERMO MAZZOLINI

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Investigaciones Clínicas; 2022

Introduction: Liver cirrhosis involves chronic damage, wound healingand fibrogenic processes. Mesenchymal stem cells (MSC)-derivedextracellular vesicles (EVs) are an interesting therapeutic optionfor regenerative medicine. Aim: To compare EVs derived fromdifferent clinical relevant sources of MSC as therapeutic tool for liverfibrosis. Methods: EVs were isolated by ion exchange chromatographyfrom supernatants of adipose tissue MSCs (ASC-EV), inducedpluripotent stem cells-derived MSCs- (iMSC-EV), and umbilical cordperivascular cells (HUCPVC-EV). EVs isolation was confirmed byprotein (BCA) and CD63 (ELISA) quantification and markers expression(CD9, CD81) by flow cytometry. In vitro effects of EVs on hepaticstellate cells (HSC) pro-fibrogenic genes expression (Col1A2and a-SMA) were evaluated in CFSC-G2 cell line by qPCR. Antifibroticeffect of EVs was determined in experimental mice model ofliver fibrosis (thioacetamide for 8 weeks in BALB/c mice). On week6, ASC-EV, iMSCs-EV and HUCPVC-EV were i.v. injected every 5days for a total of 3 doses. At week 8, animals were sacrificed, andliver samples analyzed. Collagen deposition was measured by Siriusred staining; immunohistochemistry for PCNA proliferating cells, anda-SMA (a-smooth muscle actin) for activated HSC was performed.Results: The three MSC source produce significant amount of EVswith typical surface markers CD9, CD63 and CD81. In vitro HSCincubation with EVs from different MSC sources down-regulates insimilar levels the Col1a2 (p