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Cell\u2010based and cell\u2010free\u2010based therapies have proven to be effective in treating ALF; however, their clinical application is limited by cell tumorigenicity and extracellular vesicle (EV) isolation in large doses. Here, we explored the effectiveness and mechanism of umbilical cord mesenchymal stem cells (hUCMSCs)\u2010based bioartificial liver (hUCMSC\u2010BAL), which is a simple and efficient strategy for ALF. D\u2010galactosamine\u2010based pig and mouse ALF models were used to explore the effectiveness of hUCMSC\u2010BAL and hUCMSC\u2010sEV therapies. Furthermore, high\u2010throughput sequencing, miRNA transcriptome analysis, and western blot were performed to clarify whether the miR\u2010139\u20105p\/PDE4D axis plays a critical role in the ALF model in vivo and in vitro. hUCMSC\u2010BAL significantly reduced inflammatory responses and cell apoptosis. hUCMSC\u2010sEV significantly improved liver function in ALF mice and enhanced the regeneration of liver cells. Furthermore, hUCMSC\u2010sEV miRNA transcriptome analysis showed that miR\u2010139\u20105p had the highest expression and that PDE4D was one of its main target genes. The sEV miR\u2010139\u20105p\/PDE4D axis played a role in the treatment of ALF by inhibiting cell apoptosis. Our data indicate that hUCMSC\u2010BAL can inhibit cytokine storms and cell apoptosis through the sEV miR\u2010139\u20105p\/PDE4D axis. Therefore, we propose hUCMSC\u2010BAL as a therapeutic strategy for patients with early ALF.<\/jats:p>","DOI":"10.1002\/btm2.10552","type":"journal-article","created":{"date-parts":[[2023,6,3]],"date-time":"2023-06-03T02:40:10Z","timestamp":1685760010000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A simple and efficient strategy for cell\u2010based and cell\u2010free\u2010based therapies in acute liver failure:\n                    <scp>hUCMSCs<\/scp>\n                    bioartificial liver"],"prefix":"10.1002","volume":"8","author":[{"given":"Lei","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery II, Zhujiang Hospital Southern Medical University  Guangzhou Guangdong China"},{"name":"Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative 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