Human liver stem cells express UGT1A1 and improve phenotype of immunocompromised Crigler Najjar syndrome type I mice(241 views) Famulari ES, Navarro-tableros V, Herrera Sanchez MB, Bortolussi G, Gai M, Conti L, Silengo L, Tolosano E, Tetta C, Muro AF, Camussi G, Fagoonee S, Altruda F
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
2i3T - Societa per la gestione dell'incubatore di imprese e per il trasferimento tecnologico dell'Universita degli studi di Torino, Scarl and Molecular Biotechnology Center, Turin, Italy.
International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
Institute of Biostructure and Bioimaging, CNR c/o Molecular Biotechnology Center, Turin, Italy.
Unicyte srl, Turin, Italy.
Department of Medical Sciences, University of Turin, Turin, Italy.
0000 0001 2336 6580grid.7605.4Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy
0000 0004 1759 4810grid.425196.dInternational Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
2i3T - Società per la gestione dell'incubatore di imprese e per il trasferimento tecnologico dell'Università degli studi di Torino, Scarl and Molecular Biotechnology Center, Turin, Italy.
References: Not available.
Human liver stem cells express UGT1A1 and improve phenotype of immunocompromised Crigler Najjar syndrome type I mice
Crigler Najjar Syndrome type I (CNSI) is a rare recessive disorder caused by mutations in the Ugt1a1 gene. There is no permanent cure except for liver transplantation, and current therapies present several shortcomings. Since stem cell-based therapy offers a promising alternative for the treatment of this disorder, we evaluated the therapeutic potential of human liver stem cells (HLSC) in immune-compromised NOD SCID Gamma (NSG)/Ugt1−/− mice, which closely mimic the pathological manifestations in CNSI patients. To assess whether HLSC expressed UGT1A1, decellularised mouse liver scaffolds were repopulated with these cells. After 15 days’ culture ex vivo, HLSC differentiated into hepatocyte-like cells showing UGT1A1 expression and activity. For the in vivo human cell engraftment and recovery experiments, DiI-labelled HLSC were injected into the liver of 5 days old NSG/Ugt1−/− pups which were analysed at postnatal Day 21. HLSC expressed UGT1A1 in vivo, induced a strong decrease in serum unconjugated bilirubin, thus significantly improving phenotype and survival compared to untreated controls. A striking recovery from brain damage was also observed in HLSC-injected mutant mice versus controls. Our proof-of-concept study shows that HLSC express UGT1A1 in vivo and improve the phenotype and survival of NSG/Ugt1−/− mice, and show promises for the treatment of CNSI.
Human liver stem cells express UGT1A1 and improve phenotype of immunocompromised Crigler Najjar syndrome type I mice
No results.
Human liver stem cells express UGT1A1 and improve phenotype of immunocompromised Crigler Najjar syndrome type I mice
Kim YH, Shin SW, Pellicano R, Fagoonee S, Choi IJ, Kim YI, Park B, Choi JM, Kim SG, Choi J, Park JY, Oh S, Yang HJ, Lim JH, Im JP, Kim JS, Jung HC, Ponzetto A, Figura N, Malfertheiner P, Choi IJ, Kook MC, Kim YI, Cho SJ, Lee JY, Kim CG, Park B, Nam BH, Bae SE, Choi KD, Choe J, Kim SO, Na HK, Choi JY, Ahn JY, Jung KW, Lee J, Kim DH, Chang HS, Song HJ, Lee GH, Jung HY, Seta T, Takahashi Y, Noguchi Y, Shikata S, Sakai T, Sakai K, Yamashita Y, Nakayama T, Leja M, Park JY, Murillo R, Liepniece-karele I, Isajevs S, Kikuste I, Rudzite D, Krike P, Parshutin S, Polaka I, Kirsners A, Santare D, Folkmanis V, Daugule I, Plummer M, Herrero R, Tsukamoto T, Nakagawa M, Kiriyama Y, Toyoda T, Cao X, Corral JE, Mera R, Dye CW, Morgan DR, Lee YC, Lin JT, Garcia Martin R, Matia Cubillo A, Lee SH, Park JM, Han YM, Ko WJ, Hahm KB, Leontiadis GI, Ford AC, Ichinose M, Sugano K, Jeong M, Park JM, Han YM, Park KY, Lee DH, Yoo JH, Cho JY, Hahm KB, Bang CS, Baik GH, Shin IS, Kim JB, Suk KT, Yoon JH, Kim YS, Kim DJ * Helicobacter pylori Eradication for Prevention of Metachronous Recurrence after Endoscopic Resection of Early Gastric Cancer(667 views) N Engl J Med (ISSN: 0028-4793, 0028-4793linking, 1533-4406electronic), 2015 Jun; 30642104201566393291: 749-756. Impact Factor:59.558 ViewExport to BibTeXExport to EndNote