Abstract: Methods are disclosed herein for efficiently generating human induced pluripotent stem cells (iPSC) containing a nucleic acid including a doxycycline promoter operably linked to a nucleic acid encoding Cas9. These methods include transfecting a human somatic cell with a nucleic acid molecule comprising a doxycycline promoter operably linked to a nucleic acid encoding a Cas9, and constitutive promoter operably linked to a tetracycline responsive element and inducing the somatic cell to form an iPSC, thereby producing an iPSC that can undergo CRISPR/Cas9-mediated recombination at a high efficiency. The human iPSC, or a cell differentiated therefrom, is cultured in the presence of doxycycline to induce expression of the Cas9. These cells can then be used to target in any gene of interest by introducing nucleic acids encoding sgRNAs. Induced pluripotent stem cells produced by these methods are also disclosed.

Abstract: Methods are disclosed herein for producing human hepatocytes from human induced pluripotent stem cells. Also provided are transgenic rats for the expansion of human hepatocytes, such as those produced using the methods disclosed herein.

Abstract: Disclosed are compositions and methods for treating a liver disease in a subject by increasing transport or retention of HNF4?, a transcriptional factor, into a nucleus of a hepatocyte in the subject. In some embodiments, the method comprises upregulating expression or function of one or more transcription factors selected from the group consisting of PROX1, NR5A2, NROB2, MTF1, SREBP1, EP300, and POM121C, and functional fragments thereof, and/or downregulating expression or function of one or more transcription factors DNAJB 1/F1SP40, ATF6, ATF4, and PERK, and functional fragments thereof.

Abstract: One aspect of the invention provides a method for harvesting adult cells from an organ. The method includes perfusing the organ with a perfusate and isolating adult cells from the organ, thereby harvesting the adult cells from the organ. Another aspect of the invention provides a method for rehabilitating an organ. The method includes: dividing the organ into a first portion and a second portion, perfusing the first portion with a decellularization medium, isolating adult cells from the second portion, and recellularizing the first portion with a suspension of the adult cells, thereby rehabilitating the organ.

Abstract: One aspect of the invention provides a method for harvesting adult cells from an organ. The method includes perfusing the organ with a perfusate and isolating adult cells from the organ, thereby harvesting the adult cells from the organ. Another aspect of the invention provides a method for rehabilitating an organ. The method includes: dividing the organ into a first portion and a second portion, perfusing the first portion with a decellularization medium, isolating adult cells from the second portion, and recellularizing the first portion with a suspension of the adult cells, thereby rehabilitating the organ.

Abstract: Methods are disclosed herein for producing human hepatocytes from human induced pluripotent stem cells. Also provided are transgenic rats for the expansion of human hepatocytes, such as those produced using the methods disclosed herein.

Abstract: Methods are disclosed herein for efficiently generating human induced pluripotent stem cells (iPSC) containing a nucleic acid including a doxycycline promoter operably linked to a nucleic acid encoding Cas9. These methods include transfecting a human somatic cell with a nucleic acid molecule comprising a doxycycline promoter operably linked to a nucleic acid encoding a Cas9, and constitutive promoter operably linked to a tetracycline responsive element and inducing the somatic cell to form an iPSC, thereby producing an iPSC that can undergo CRISPR/Cas9-mediated recombination at a high efficiency. The human iPSC, or a cell differentiated therefrom, is cultured in the presence of doxycycline to induce expression of the Cas9. These cells can then be used to target in any gene of interest by introducing nucleic acids encoding sgRNAs. Induced pluripotent stem cells produced by these methods are also disclosed.

Abstract: The presently disclosed invention is directed to the discovery that hepatocyte nuclear factor 4 alpha (HNF4?; also known as NR2A1), a transcription factor, reverses hepatocyte dysfunction in an animal model of cirrhosis, resulting in improvement in hepatic function, treatment of cirrhosis, and prolonged survival.

Abstract: Provided herein are methods or making and using whole or partial organ ECM structures comprising an anticoagulant. Also provided are organ structures prepared according to those methods.

Abstract: One aspect of the invention provides a method for harvesting adult cells from an organ. The method includes perfusing the organ with a perfusate and isolating adult cells from the organ, thereby harvesting the adult cells from the organ. Another aspect of the invention provides a method for rehabilitating an organ. The method includes: dividing the organ into a first portion and a second portion, perfusing the first portion with a decellularization medium, isolating adult cells from the second portion, and recellularizing the first portion with a suspension of the adult cells, thereby rehabilitating the organ.

Abstract: The presently disclosed invention is directed to the discovery that hepatocyte nuclear factor 4 alpha (HNF4?; also known as NR2A1), a transcription factor, reverses hepatocyte dysfunction in an animal model of cirrhosis, resulting in improvement in hepatic function, treatment of cirrhosis, and prolonged survival.

Abstract: One aspect of the invention provides a method for harvesting adult cells from an organ. The method includes perfusing the organ with a perfusate and isolating adult cells from the organ, thereby harvesting the adult cells from the organ. Another aspect of the invention provides a method for rehabilitating an organ. The method includes: dividing the organ into a first portion and a second portion, perfusing the first portion with a decellularization medium, isolating adult cells from the second portion, and recellularizing the first portion with a suspension of the adult cells, thereby rehabilitating the organ.