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Inoue Y, Kawahara H, Shirahata S, Sugimoto Y: Retinoic acid improves a hybridoma culture in a fructose-based medium by up-regulation of fructose incorporation via retinoid nuclear receptors. Biosci Biotechnol Biochem. 2006 Sep;70(9):2248-53. Epub 2006 Sep 7. Fructose was focused on as an alternative sugar source to glucose in a hybridoma culture medium because it decreases lactate production during cultivation, leading to cell and product stability. But, not all human hybridoma cell lines grew well in a fructose-based serum-free medium. We found that the addition of all-trans-retinoic acid to the fructose-based medium improved the growth and monoclonal antibody production of hybridoma cell lines by up-regulation of fructose incorporation that represented increased expression of the fructose transporter, GLUT5. Selective activation of retinoid nuclear receptor by synthetic ligands showed that both retinoic acid receptors and retinoid X receptors might be related to the improvement of the fructose-based hybridoma culture. This study might be applicable to cell cultures susceptible to lactate and pH changes as well as hybridoma cultures. |
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