Intrahepatic Administration of Human Liver Stem Cells in Infants with Inherited Neonatal-Onset Hyperammonemia: A Phase I Study

• DOI: 10.1007/s12015-019-09925-z
• Publication Date: 2019-12-02T11:42:29Z
• Authors: Marco Spada; Francesco Porta; Dorico Righi; Carlo Gazzera; Francesco Tandoi; Ivana Ferrero; Franca Fagioli; Maria Beatriz Her...; Pier Luigi Calvo; Elisa Biamino; Stefania Bruno; Monica Gunetti; Cristina Contursi; Carola Lauritano; Alessandra Conio; Antonio Amoroso; Mauro Salizzoni; Lorenzo Silengo; Giovanni Camussi; Renato Romagnoli
• Keywords: Hyperammonemia; Methylmalonic acidemia; Immunosuppression; Decompensation

Abstract Previous studies have shown that human liver stem-like cells (HLSCs) may undergo differentiation in vitro into urea producing hepatocytes and vivo sustain function models of experimentally induced acute injury. The aim this study was to assess the safety HLSCs intrahepatic administration inherited neonatal-onset hyperammonemia. approved by Agenzia Italiana del Farmaco on favorable opinion Italian Institute Health as an open-label, prospective, uncontrolled, monocentric Phase I (HLSC 01–11, EudraCT-No. 2012–002120-33). Three patients affected argininosuccinic aciduria (patient 1) methylmalonic acidemia (patients 2 3) included transplantation list were enrolled. In all patients, administered percutaneous injections (once a week for two consecutive weeks) within first months life. patient received 125,000 x gram liver/dose while other twice dose. No immunosuppression since possess immunomodulatory activities. None experienced infections, hyperammonemia decompensation, or adverse events during whole observation period. donor specific antibodies (DSA) against detected. Patients metabolic stable despite increase (~30%) protein intake. Two underwent after 19 11 respectively, explantation, native livers showed no histological alterations. conclusion, safe newborn with These data pave way II selected acquired disorders.