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Evaluating effects of L-carnitine on human bone-marrow-derived mesenchymal stem cells

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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.

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Abbreviations

ADSCs:

Adipose-derived stem cells

BmMSC:

Bone-marrow-derived mesenchymal stem cell

MSCs:

Mesenchymal stem cells

SAGE:

Serial analysis of gene expression

SREBF:

Sterol regulatory element binding transcription factor

VDAC:

Voltage-dependent anion channel

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Acknowledgements

This work is financially supported by the Adaptable and Seamless Technology Transfer Program through target-driven R&D from the Japan Science, Technology Agency (JST) and by the Japan Agency for Medical Research and Development (AMED), the project of realization of regenerative medicine and highway. The authors thank Ms. M. Yamada, Ms. K. Ota, Ms. H. Kurose, Ms. R. Mochizuki, Ms. Y. Fukusumi and Ms. I. Fujimoto for their technical assistance.

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Authors and Affiliations

  1. Center for Regenerative Medicine, Yamaguchi University School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan

    Koichi Fujisawa & Isao Sakaida

  2. Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan

    Koichi Fujisawa, Taro Takami, Yumi Fukui, Luiz Fernando Quintanilha, Toshihiko Matsumoto, Naoki Yamamoto & Isao Sakaida

Authors
  1. Koichi Fujisawa
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  2. Taro Takami
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  3. Yumi Fukui
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  4. Luiz Fernando Quintanilha
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  5. Toshihiko Matsumoto
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  6. Naoki Yamamoto
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  7. Isao Sakaida
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Corresponding author

Correspondence to Taro Takami.

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Contribution

K.F., T.T. and I.S. conceived and designed the experiments. K.F. performed the experiments. T.M., N.Y. and L.Q. analyzed the data. Y.F and T.T. contributed reagents/materials/analysis tools. K.F. and T.T. wrote the paper.

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The authors declare that they have no financial conflict of interest.

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Supplemental Fig. 1

Evaluation of long-term effects of L-carnitine on proliferation of BmMSCs (Passage 1). Measurement of effect of L-carnitine on proliferation by using an Incucyte system. Data are presented as averages ± standard error. L-carnitine was added to cultures of mononuclear cells (passage 0) to passage 1 for 20 days. (GIF 159 kb)

High resolution image (TIF 50 kb)

Supplemental Fig. 2

Evaluation of long-term effects of L-carnitine on apoptosis of BmMSCs. Effect of L-carnitine in suppressing doxorubicin-induced apoptosis. L-carnitine was added to cultures of mononuclear cells (passage 0) to passage 1. Passage 1 MSC was used for addition of doxorubicin. The effect was evaluated by measuring caspase-3/7 activities at 24 h after doxorubicin was added. *P < 0.05 (GIF 185 kb)

High resolution image (TIF 39 kb)

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Fujisawa, K., Takami, T., Fukui, Y. et al. Evaluating effects of L-carnitine on human bone-marrow-derived mesenchymal stem cells. Cell Tissue Res 368, 301–310 (2017). https://doi.org/10.1007/s00441-017-2569-0

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  • DOI: https://doi.org/10.1007/s00441-017-2569-0

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