Subject(s)
Celiac Disease , Ileum , Humans , Ileum/diagnostic imaging , Ileum/surgery , Ileum/pathology , Intestinal Mucosa/pathology , Atrophy , Celiac Disease/pathologySubject(s)
Humans , Male , Aged , Biopsy , Suction , Gastrointestinal Diseases , Digestive System Neoplasms , GastroenterologySubject(s)
Scleroderma, Systemic , Endoscopy , Humans , Intestines , Scleroderma, Systemic/complicationsSubject(s)
Barrett Esophagus , Esophageal Neoplasms , Aged , Barrett Esophagus/diagnosis , Esophagus/diagnostic imaging , Humans , Male , MetaplasiaSubject(s)
Antihypertensive Agents , Colitis, Lymphocytic , Colitis, Microscopic , Imidazoles , Tetrazoles , Antihypertensive Agents/adverse effects , Biopsy , Colitis, Lymphocytic/chemically induced , Colonoscopy , Diarrhea , Humans , Imidazoles/adverse effects , Practice Guidelines as Topic , Tetrazoles/adverse effectsABSTRACT
Increasing markets for biopharmaceuticals, including monoclonal antibodies, have triggered a permanent need for bioprocess optimization. Biochemical engineering approaches often include the optimization of basal and feed media to improve productivities of Chinese hamster ovary (CHO) cell cultures. Often, l-tyrosine is added as dipeptide to deal with its poor solubility at neutral pH. Showcasing IgG1 production with CHO cells, we investigated the supplementation of three l-tyrosine (TYR, Y) containing dipeptides: glycyl-l-tyrosine (GY), l-tyrosyl-l-valine (YV), and l-prolyl-l-tyrosine (PY). While GY and YV led to almost no phenotypic and metabolic differences compared to reference samples, PY significantly amplified TYR uptake thus maximizing related catabolic activity. Consequently, ATP formation was roughly four times higher upon PY application than in reference samples.
ABSTRACT
The improvement of cell specific productivities for the formation of therapeutic proteins is an important step towards intensified production processes. Among others, the induction of the desired production phenotype via proper media additives is a feasible solution provided that said compounds adequately trigger metabolic and regulatory programs inside the cells. In this study, S-(5'-adenosyl)- l-methionine (SAM) and 5'-deoxy-5'-(methylthio)adenosine (MTA) were found to stimulate cell specific productivities up to approx. 50% while keeping viable cell densities transiently high and partially arresting the cell cycle in an anti-IL-8-producing CHO-DP12 cell line. Noteworthy, MTA turned out to be the chemical degradation product of the methyl group donor SAM and is consumed by the cells.
Subject(s)
Antibodies , CHO Cells/drug effects , Culture Media/pharmacology , Deoxyadenosines/pharmacology , S-Adenosylmethionine/pharmacology , Thionucleosides/pharmacology , Animals , Antibodies/analysis , Antibodies/metabolism , Cell Cycle/drug effects , Cricetinae , Cricetulus , Culture Media/chemistry , Recombinant Proteins/analysis , Recombinant Proteins/metabolismABSTRACT
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