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An efficient and convenient protocol for generation of human iPSC-derived hepatocytes

Novel marker for liver progenitor cells identified

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Institute of Molecular and Cellular Biosciences
2015/10/29

© 2015 Taketomo Kido.(Above) Expression of CPM during liver development (Below) Generation of hepatocytes and cholangiocytes from hiPSC-derived CPM+ liver progenitor cells.

CPM expression on liver progenitor cells
(Above) Expression of CPM during liver development (Below) Generation of hepatocytes and cholangiocytes from hiPSC-derived CPM+ liver progenitor cells.
© 2015 Taketomo Kido.

Researchers at the University of Tokyo have developed an efficient and cheap protocol for production of human iPS cell-derived liver cells. The liver cells derived by this method show characteristics of mature liver cells over a long period so may find applications in drug toxicity tests, the search for new drugs and cell therapy.

The liver is a central organ for metabolism, and hepatocytes, the major type of liver cell, play key roles in liver function by producing numerous metabolic enzymes. To date, there are many studies reporting differentiation of human induced pluripotent stem cells (hiPSCs) to hepatocytes, but an efficient and convenient protocol for production of mature hepatocytes has yet to be established.

Assistant Professor Taketomo Kido, Professor Atsushi Miyajima and their research group at the Laboratory of Cell Growth and Differentiation in the Institute of Molecular and Cellular Biosciences have established a technique to isolate hiPSC-derived liver progenitor cells (LPCs, cells which develop into hepatocytes) based on the expression of single cell surface marker. The marker identified by the research group, the protein carboxypeptidase M (CPM), is found in embryonic LPCs and decreases in amount as the hepatocytes mature, indicating that it may be a useful marker for separation of LPCs from differentiating hiPSCs. They also successfully developed a simple method to isolate the CPM+ LPCs from hiPSC-derived cells at the immature hepatocyte stage. Furthermore, the group also found that CPM+ LPCs differentiated into both hepatocytes and cholangiocytes (bile duct epithelial cells).

“The CPM+ LPCs that we have derived from human iPSCs can be transferred from one medium to another for continuous culture or frozen to preserve them,” says Assistant Professor Kido. He continues, “These cells exhibit the characteristics of mature hepatocytes for more than two weeks, making them useful for applications in drug discovery and toxicology.”

This study was supported by CREST program of Japan Agency for Medical Research and Development, and Grants-in-Aid for Scientific Research of Japan Society for the Promotion of Science.

Press release (Japanese)

Paper

Taketomo Kido, Yuta Koui, Kaori Suzuki, Ayaka Kobayashi, Yasushi Miura, Edward Y. Chern, Minoru Tanaka, Atsushi Miyajima, "CPM is a useful cell surface marker to isolate expandable bi-potential liver progenitor cells derived from human iPS cells", Stem Cell Reports Vol.5/1-8: 2015/9/11 (Japan time), doi: 10.1016/j.stemcr.2015.08.008.
Article link (Publication)

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Institute of Molecular and Cellular Biosciences

Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences

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