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Previously, we obtained <jats:styled-content style=\"fixed-case\">HLC<\/jats:styled-content>s from human umbilical cord\u2010derived <jats:styled-content style=\"fixed-case\">MSC<\/jats:styled-content>s by overexpressing seven micro<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s (<jats:styled-content style=\"fixed-case\">HLC<\/jats:styled-content>\u20107) and characterized their liver functions <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Here, we aimed to screen out the optimal mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> candidates for hepatic differentiation. We sequentially removed individual mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s from the pool and examined the effect of transfection with remainder using <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>, periodic acid\u2014Schiff (<jats:styled-content style=\"fixed-case\">PAS<\/jats:styled-content>) staining and low\u2010density lipoprotein (<jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>) uptake assays and by assessing their function in liver injury models. Surprisingly, miR\u201030a and miR\u20101290 were dispensable for hepatic differentiation. The remaining five mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s (miR\u2010122, miR\u2010148a, miR\u2010424, miR\u2010542\u20105p and miR\u20101246) are essential for this process, because omitting any one from the five\u2010mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> combination prevented hepatic trans\u2010differentiation. We found that <jats:styled-content style=\"fixed-case\">HLC<\/jats:styled-content>s trans\u2010differentiated from five micro<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s (<jats:styled-content style=\"fixed-case\">HLC<\/jats:styled-content>\u20105) expressed high level of hepatic markers and functioned similar to hepatocytes. Intravenous transplantation of <jats:styled-content style=\"fixed-case\">HLC<\/jats:styled-content>\u20105 into nude mice with <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>\u2010induced fulminant liver failure and acute liver injury not only improved serum parameters and their liver histology, but also improved survival rate of mice in severe hepatic failure. These data indicated that <jats:styled-content style=\"fixed-case\">HLC<\/jats:styled-content>\u20105 functioned similar to <jats:styled-content style=\"fixed-case\">HLC<\/jats:styled-content>\u20107 <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, which have been shown to resemble hepatocytes. Instead of using seven\u2010mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> combination, a simplified five\u2010mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> combination can be used to obtain functional <jats:styled-content style=\"fixed-case\">HLC<\/jats:styled-content>s in only 7 days. Our study demonstrated an optimized and efficient method for generating functional <jats:styled-content style=\"fixed-case\">MSC<\/jats:styled-content>\u2010derived <jats:styled-content style=\"fixed-case\">HLC<\/jats:styled-content>s that may serve as an attractive cell alternative for BALSS.<\/jats:p>","DOI":"10.1111\/jcmm.13027","type":"journal-article","created":{"date-parts":[[2016,11,22]],"date-time":"2016-11-22T10:28:42Z","timestamp":1479810522000},"page":"881-893","source":"Crossref","is-referenced-by-count":43,"title":["Induction of hepatocyte\u2010like cells from human umbilical cord\u2010derived mesenchymal stem cells by defined microRNAs"],"prefix":"10.1111","volume":"21","author":[{"given":"Xia","family":"Zhou","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cancer Biology Xijing Hospital of Digestive Diseases The Fourth Military Medical University Xi'an Shaanxi Province 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