| http://purl.uniprot.org/citations/34382351 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34382351 | http://www.w3.org/2000/01/rdf-schema#comment | "Although liver-humanized animals are desirable tools for drug development and expansion of human hepatocytes in large quantities, their development is restricted to mice. In animals larger than mice, a precondition for efficient liver humanization remains preliminary because of different xeno-repopulation kinetics in livers of larger sizes. Since rats are ten times larger than mice and widely used in pharmacological studies, liver-humanized rats are more preferable. Here, Fah-/- Rag2-/- IL2rg-/- (FRG) rats are generated by CRISPR/Cas9, showing accelerated liver failure and lagged liver xeno-repopulation compared to FRG mice. A survival-assured liver injury preconditioning (SALIC) protocol, which consists of retrorsine pretreatment and cycling 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) administration by defined concentrations and time intervals, is developed to reduce the mortality of FRG rats and induce a regenerative microenvironment for xeno-repopulation. Human hepatocyte repopulation is boosted to 31 ± 4% in rat livers at 7 months after transplantation, equivalent to approximately a 1200-fold expansion. Human liver features of transcriptome and zonation are reproduced in humanized rats. Remarkably, they provide sufficient samples for the pharmacokinetic profiling of human-specific metabolites. This model is thus preferred for pharmacological studies and human hepatocyte production. SALIC may also be informative to hepatocyte transplantation in other large-sized species."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.org/dc/terms/identifier | "doi:10.1002/advs.202101188"xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Oda T."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Furuya K."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Fan J."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Fang M."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Hui L."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Li D."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Ma X."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Pan G."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Sun Z."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Wang C."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Shao Y."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Wu B."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Peng Z."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Zheng Y.W."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Ohkohchi N."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/author | "Ge J.Y."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/name | "Adv Sci (Weinh)"xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/pages | "e2101188"xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/title | "Survival-Assured Liver Injury Preconditioning (SALIC) Enables Robust Expansion of Human Hepatocytes in Fah-/- Rag2-/- IL2rg-/- Rats."xsd:string |
| http://purl.uniprot.org/citations/34382351 | http://purl.uniprot.org/core/volume | "8"xsd:string |