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This study by Tamai et al. explores the recapitulation of the urea cycle in vitro using a liver model derived from murine embryonic stem cells. The research investigates the enzymatic activities involved in urea synthesis and assesses cell viability and metabolite levels throughout the culture periods. By utilizing specific substrates and measuring enzymatic releases, the study provides insights into the functional properties of stem cell-derived hepatocytes. The findings aim to advance the understanding of liver function and potential applications in regenerative medicine and metabolic disorder modeling.
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Amino acid In vitro recapitulation of the urea cycle using murine embryonic stem cellderived in vitro liver model Miho Tamai, Mami Aoki, Akihito Nishimura, Koji Morishita, and Yoh-ichi Tagawa* *To whom correspondence should be addressed: Yoh-ichiTagawa, Email: ytagawa@bio.titech.ac.jp, Tel.: +81 45-924-5791. Fax: +81 45-924-5815. Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology 4.5 3.0 Urea (mM) 1.5 0 [day] 1 4 7 1 4 7 On collagen On EHS gel Supplementary Fig. S1 Day of Culture(day) B A Isolated Hepatocyte Day of Culture (day) Adult Liver On collagen On EHS gel 1 4 7 1 4 7 [day] cps1 otc arg1 ornt1 hprt
Supplementary Fig. S2 150 100 50 B A 0 * * Released Enzymes (IU/L) Cell Viability (%) - - - - + + L-Ornithine L-Ornithine - - + + + + Ethanol Ethanol C D * * 5.0 NH4+ (mM) 2.5 Urea (mM) 0 - - - - + + L-Ornithine L-Ornithine - - + + + + Ethanol Ethanol