title: Evaluating effects of L-carnitine on human bone-marrow-derived mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) are multipotent cells showing potential for use in regenerative medicine. Culture techniques that are more stable and methods for the more efficient production of MSCs with therapeutic efficacy are needed. We evaluate the effects of growing bone marrow (Bm)-derived MSCs in the presence of L-carnitine, which is believed to promote lipid metabolism and to suppress apoptosis. The presence of L-carnitine decreased the degree of drug-induced apoptosis and suppressed adipogenic differentiation. Metabolomic analysis by means of the exhaustive investigation of metabolic products showed that, in addition to increased β-oxidation and the expression of all carnitine derivatives other than deoxycarnitine (an intermediate in carnitine synthesis), polysaturated and polyunsaturated acids were down-regulated. An integrated analysis incorporating both serial analysis of gene expression and metabolomics revealed increases in cell survival, suggesting the utility of carnitine. The addition of carnitine elevated the oxygen consumption rate by BmMSCs that had been cultured for only a few generations and those that had become senescent following repeated replication indicating that mitochondrial activation occurred. Our exhaustive analysis of the effects of various carnitine metabolites thus suggests that the addition of L-carnitine to BmMSCs during expansion enables efficient cell production.
authors.affiliation: Center for Regenerative Medicine, Yamaguchi University School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan.|Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Fujisawa
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan. t-takami@yamaguchi-u.ac.jp.
authors.forename: Taro
authors.initials: T
authors.lastname: Takami
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Fukui
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan.
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Quintanilha
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Center for Regenerative Medicine, Yamaguchi University School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan.|Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002331:Carnitine / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D055432:Metabolomics; D058977:Molecular Sequence Annotation; D010101:Oxygen Consumption / Q000187:drug effects; D025341:Principal Component Analysis
chemical_list: D005227:Fatty Acids; D002331:Carnitine
keywords: Apoptosis; Fatty acid; Metabolomics; Microarray; Mitochondria