Therapeutic effect of human umbilical cord perivascular cells-derived extracellular vesicles engineered to produce IGF-I on liver fibrosis in mice.

DOMÍNGUEZ L; ATORRASAGASTI C; CANTERO MJ; FIORE E; BAYO J; RODRIGUEZ M; GARCIA M; MAZZOLINI G; MALVICINI M.; ONORATO A; YANNARELLI G

Mar del Plata

Congreso; LXIII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

Sociedad Argentina de Investigación Clínica (SAIC)

Introduction:Liver cirrhosis involves chronic damage, wound healing and fibrogenicprocesses. Human umbilical cord perivascular cells (HUCPVs) are a type ofmesenchymal stromal cells (MSCs) obtained from birth-associated tissues. MSCs supporttissues repair and modulate the inflammatory process. Particularly,extracellular vesicles (EVs) could mediate MSCs paracrine effects. Wepreviously demonstrated that bone marrow-derived MSCs engineering to produceInsulin Growth Factor like-I (IGF-I) ameliorate liver fibrosis in mice.We aimedto evaluate the therapeutic effect of HUCPVs engineered to produce IGF-I andthe role of EVs in experimental liver fibrosis. Methods:HUCPVs were infected with adenoviruses codifying for human IGF-I (AdIGF‑I) orgreen fluorescence protein (AdGFP) and EVs were isolated from supernatantsafter 3 days of infection by differential centrifugation. EVs characterizationwas performed by protein quantification, CD63 and internal IGF-I expression. Fibrosiswas induced in BALB/c mice by chronic administration of thioacetamide (TAA)during 8 weeks. On week 6, cells (AdIGF-I-HUCPVs or AdGFP-HUCPVs; dose: 5x10E5cells), EVs (EVs‑HUCPVs, EVs-HUCPVs-AdIGF-I or EVs-HUCPVs-AdGFP, 3 doses, 15mg/dose/mice every 5 days)or saline were intravenously administered. Animals were sacrificed at week 8 tocollect liver samples. Results:The application of AdIGF-I-HUCPVs resulted in a further amelioration of liverfibrosis when compared to AdGFP-HUCPVs (p