Yissum - Research Development Company of the Hebrew University

Method to Differentiate Metabolically Functional Human Hepatocytes from Pluripotent Stem Cells

Posted by Yissum - Research Development Company of the Hebrew UniversityResponsive · Innovative Products and Technologies · Israel

Summary of the technology

Method to differentiate metabolically functional hepatocytes from pluripotent stem cells or fetal tissue
Project ID : 6-2016-4294

Yissum - Research Development Company of the Hebrew University

Description of the technology

Category

LifeSciences and BioTechnology

Application

Primary human hepatocytes are isolated from organs rejected from transplantation. Cells are expensive, show massive batch-to-batch variability and fail to proliferate in culture. Hepatocytes are routinely used by the pharmaceutical industry for drug development and toxicological studies.

Human pluripotent stem cell-derived hepatocytes offer a solution due to their minimal variability, high repeatability and lower costs. However, current stem cell-derived hepatocytes show immature fetal function (e.g. AFP), minimal drug metabolism and marginal correlation of toxicity compared to primary cells (R2=0.19).

Our Innovation

Our patent-protected methods shows:

  • 90% hepatocytes in 16-18 days
  • Double mitochondrial mass and energetic, rather than glycolytic function
  • CYP450 induction up to 80-fold on mRNA level (3A4, 1A2, 2B1)
  • Accurate toxic evaluation of steatosis and cholestasis
  • Strong correlation of toxicity compared to primary hepatocytes (R2=0.94)

Technology

We discovered the last step in human liver development and used it to create the first truly functional pluripotent stem cell-derived hepatocytes. Our method and protocol has been validated by several groups. The technology can be used to create a kit that allows the pharmaceutical industry to produce cells from their own cell lines, or to produce stem cell-derived hepatocytes to sell as frozen aliquots.

Opportunity

Human pluripotent stem cell-derived hepatocytes offer a solution due to their minimal variability, high repeatability, lower costs. However, current stem cell-derived hepatocytes show immature fetal function (e.g. AFP), minimal drug metabolism and marginal correlation of toxicity compared to primary cells (R2=0.19).

Our method produces truly functional pluripotent stem cell-derived hepatocytes. The cells show minimal fetal markers (e.g. AFP, CYP3A7), strong 80-fold CYP450 induction in response to Rifampicin, CITCO and Omeprazole, and toxicological screening values comparable to primary hepatocytes with minimal variability.

Y. Avior, G. Levy, M. Zimerman D. Kitsberg, R. Schwartz, R. Sadeh, A. Moussaieff, M. Cohen, J. Itskovitz-Eldor, Y. Nahmias. Microbial-Derived Lithocholic Acid and Vitamin K2 Drive the Metabolic Maturation of Pluripotent Stem Cells Derived Hepatocytes.Hepatology 2(1): 265-78. (2015)

A. Ehrlich, M. Ayyash, S. Tsytkin, G. Levy, M. Zimerman, R. Schwartz, M. Cohen, Y. Nahmias. Microbial-Derived Fatty Acids Drive the Mitochondrial Maturation of Pluripotent Stem Cells-Derived and Fetal Hepatocytes. Submitted for publication

Project manager

Mel Larrosa
VP Business Development Healthcare

Project researchers

Yaakov Nahmias
HUJI, School of Computer Science and Engineering
Bio-Engineering

Related keywords

  • Clean Industrial Technologies
  • Other (uncategorised)
  • Life Science & Biotechnology
  • Oncology / Cancer

About Yissum - Research Development Company of the Hebrew University

Technology Transfer Office from Israel

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. Founded in 1964 to protect and commercialize the Hebrew University’s intellectual property. Ranked among the top technology transfer companies, Yissum has registered over 8,900 patents covering 2,500 inventions; has licensed out 800 technologies and has spun-off 90 companies. Products that are based on Hebrew University technologies and were commercialized by Yissum generate today over $2 Billion in annual sales.

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