Activation of cAMP (EPAC2) signaling pathway promotes hepatocyte attachment.

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School of Life Science and Technology, Tokyo Institute of Technology, 4259-B-25 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa, 226-8501, Japan.

Published: July 2023


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Article Abstract

Primary Human Hepatocyte (PHH) remains undefeated as the gold standard in hepatic studies. Despite its valuable properties, partial attachment loss due to the extraction process and cryopreservation remained the main hurdle in its application. We hypothesized that we could overcome the loss of PHH cell attachment through thawing protocol adjustment and medium composition. We reported a novel use of a medium designed for iPSC-derived hepatocytes, increasing PHH attachment on the collagen matrix. Delving further into the medium composition, we discovered that removing BSA and exposure to cAMP activators such as IBMX and Forskolin benefit PHH attachment. We found that activating EPAC2, the cAMP downstream effector, by S-220 significantly increased PHH attachment. We also found that EPAC2 activation induced bile canaliculi formation in iPS-derived hepatocytes. Combining these factors in studies involving PHH or iPS-hepatocyte culture provides promising means to improve cell attachment and maintenance of hepatic function.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390557PMC
http://dx.doi.org/10.1038/s41598-023-39712-3DOI Listing

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Activation of cAMP (EPAC2) signaling pathway promotes hepatocyte attachment.

Sci Rep

July 2023

School of Life Science and Technology, Tokyo Institute of Technology, 4259-B-25 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa, 226-8501, Japan.

Primary Human Hepatocyte (PHH) remains undefeated as the gold standard in hepatic studies. Despite its valuable properties, partial attachment loss due to the extraction process and cryopreservation remained the main hurdle in its application. We hypothesized that we could overcome the loss of PHH cell attachment through thawing protocol adjustment and medium composition.

View Article and Find Full Text PDF