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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<jats:sup>\u2212\/\u2212<\/jats:sup> 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\u2019 culture <jats:italic>ex vivo<\/jats:italic>, HLSC differentiated into hepatocyte-like cells showing UGT1A1 expression and activity. For the <jats:italic>in vivo<\/jats:italic> human cell engraftment and recovery experiments, DiI-labelled HLSC were injected into the liver of 5 days old NSG\/Ugt1<jats:sup>\u2212\/\u2212<\/jats:sup> pups which were analysed at postnatal Day 21. HLSC expressed UGT1A1 <jats:italic>in vivo<\/jats:italic>, 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 <jats:italic>versus<\/jats:italic> controls. Our proof-of-concept study shows that HLSC express UGT1A1 <jats:italic>in vivo<\/jats:italic> and improve the phenotype and survival of NSG\/Ugt1<jats:sup>\u2212\/\u2212<\/jats:sup> mice, and show promises for the treatment of CNSI.<\/jats:p>","DOI":"10.1038\/s41598-020-57820-2","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T11:02:51Z","timestamp":1579604571000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Human liver stem cells express UGT1A1 and improve phenotype of immunocompromised Crigler Najjar syndrome type I mice"],"prefix":"10.1038","volume":"10","author":[{"given":"Elvira Smeralda","family":"Famulari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Navarro-Tableros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Beatriz","family":"Herrera Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Bortolussi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Gai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1780-098X","authenticated-orcid":false,"given":"Laura","family":"Conti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Silengo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1622-2340","authenticated-orcid":false,"given":"Emanuela","family":"Tolosano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciro","family":"Tetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9628-0494","authenticated-orcid":false,"given":"Andr\u00e9s Fernando","family":"Muro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Camussi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6070-6716","authenticated-orcid":false,"given":"Sharmila","family":"Fagoonee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorella","family":"Altruda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,21]]},"reference":[{"key":"57820_CR1","doi-asserted-by":"crossref","first-page":"17960","DOI":"10.1016\/S0021-9258(17)32403-1","volume":"269","author":"PJ Bosma","year":"1994","unstructured":"Bosma, P. 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