Evaluation of the effects of ascorbic acid on metabolism of human mesenchymal stem cells
Abstract Background Mesenchymal stem cells (MSCs) are multipotent cells holding much promise for applications in regenerative medicine. However, with problems such as aging, increases in heteroploid cells, genomic instability, and reduced maintenance of stemness, more stable culturing methods and th...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-04-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-018-0825-1 |
| _version_ | 1798043828196737024 |
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| author | Koichi Fujisawa Kazusa Hara Taro Takami Sae Okada Toshihiko Matsumoto Naoki Yamamoto Isao Sakaida |
| author_facet | Koichi Fujisawa Kazusa Hara Taro Takami Sae Okada Toshihiko Matsumoto Naoki Yamamoto Isao Sakaida |
| author_sort | Koichi Fujisawa |
| collection | DOAJ |
| description | Abstract Background Mesenchymal stem cells (MSCs) are multipotent cells holding much promise for applications in regenerative medicine. However, with problems such as aging, increases in heteroploid cells, genomic instability, and reduced maintenance of stemness, more stable culturing methods and the production of MSCs with an improved therapeutic effect are desired. Ascorbic acid (AsA), which is a cofactor for a variety of enzymes and has an antioxidant effect, cannot be synthesized by certain animals, including humans. Nevertheless, little attention has been paid to AsA when culturing MSCs. Methods We analyzed the effect of adding AsA to the culture medium on the proliferation and metabolism of human MSCs by serial analysis of gene expression and metabolome analysis. Results We found that AsA promotes MSC proliferation, and is particularly useful when expanding MSCs isolated from bone marrow. Serial analysis of gene expression and metabolome analysis suggested that, due to HIF1α accumulation caused by decreased activity of the enzymes that use AsA as a coenzyme in cultures without AsA, genes downstream of HIF1α are expressed and there is a conversion to a hypoxia-mimetic metabolism. AsA promotes HIF1α breakdown and activates mitochondria, affecting cell proliferation and metabolism. Comprehensive evaluation of the effects of AsA on various metabolic products in MSCs revealed that AsA increases HIF1α hydroxylase activity, suppressing HIF1a transcription and leading to mitochondrial activation. Conclusions Adding AsA during MSC expansion leads to more efficient preparation of cells. These are expected to be important findings for the future application of MSCs in regenerative medicine. |
| first_indexed | 2024-04-11T22:54:26Z |
| format | Article |
| id | doaj.art-665a1e03c03a45378997ac34bc633b80 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-11T22:54:26Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-665a1e03c03a45378997ac34bc633b802022-12-22T03:58:29ZengBMCStem Cell Research & Therapy1757-65122018-04-019111210.1186/s13287-018-0825-1Evaluation of the effects of ascorbic acid on metabolism of human mesenchymal stem cellsKoichi Fujisawa0Kazusa Hara1Taro Takami2Sae Okada3Toshihiko Matsumoto4Naoki Yamamoto5Isao Sakaida6Center for Regenerative Medicine, Yamaguchi University School of MedicineDepartment of Gastroenterology and Hepatology, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterology and Hepatology, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterology and Hepatology, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterology and Hepatology, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterology and Hepatology, Yamaguchi University Graduate School of MedicineCenter for Regenerative Medicine, Yamaguchi University School of MedicineAbstract Background Mesenchymal stem cells (MSCs) are multipotent cells holding much promise for applications in regenerative medicine. However, with problems such as aging, increases in heteroploid cells, genomic instability, and reduced maintenance of stemness, more stable culturing methods and the production of MSCs with an improved therapeutic effect are desired. Ascorbic acid (AsA), which is a cofactor for a variety of enzymes and has an antioxidant effect, cannot be synthesized by certain animals, including humans. Nevertheless, little attention has been paid to AsA when culturing MSCs. Methods We analyzed the effect of adding AsA to the culture medium on the proliferation and metabolism of human MSCs by serial analysis of gene expression and metabolome analysis. Results We found that AsA promotes MSC proliferation, and is particularly useful when expanding MSCs isolated from bone marrow. Serial analysis of gene expression and metabolome analysis suggested that, due to HIF1α accumulation caused by decreased activity of the enzymes that use AsA as a coenzyme in cultures without AsA, genes downstream of HIF1α are expressed and there is a conversion to a hypoxia-mimetic metabolism. AsA promotes HIF1α breakdown and activates mitochondria, affecting cell proliferation and metabolism. Comprehensive evaluation of the effects of AsA on various metabolic products in MSCs revealed that AsA increases HIF1α hydroxylase activity, suppressing HIF1a transcription and leading to mitochondrial activation. Conclusions Adding AsA during MSC expansion leads to more efficient preparation of cells. These are expected to be important findings for the future application of MSCs in regenerative medicine.http://link.springer.com/article/10.1186/s13287-018-0825-1Ascorbic acidMesenchymal stem cellMeztabolomeTranscriptomeExtracellular matrixHypoxia |
| spellingShingle | Koichi Fujisawa Kazusa Hara Taro Takami Sae Okada Toshihiko Matsumoto Naoki Yamamoto Isao Sakaida Evaluation of the effects of ascorbic acid on metabolism of human mesenchymal stem cells Stem Cell Research & Therapy Ascorbic acid Mesenchymal stem cell Meztabolome Transcriptome Extracellular matrix Hypoxia |
| title | Evaluation of the effects of ascorbic acid on metabolism of human mesenchymal stem cells |
| title_full | Evaluation of the effects of ascorbic acid on metabolism of human mesenchymal stem cells |
| title_fullStr | Evaluation of the effects of ascorbic acid on metabolism of human mesenchymal stem cells |
| title_full_unstemmed | Evaluation of the effects of ascorbic acid on metabolism of human mesenchymal stem cells |
| title_short | Evaluation of the effects of ascorbic acid on metabolism of human mesenchymal stem cells |
| title_sort | evaluation of the effects of ascorbic acid on metabolism of human mesenchymal stem cells |
| topic | Ascorbic acid Mesenchymal stem cell Meztabolome Transcriptome Extracellular matrix Hypoxia |
| url | http://link.springer.com/article/10.1186/s13287-018-0825-1 |
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