Bone marrow-derived humoral factors suppress oxidative phosphorylation, upregulate TSG-6, and improve therapeutic effects on liver injury of mesenchymal stem cells

• Miyaji Takashi

  Department of Gastroenterology & Hepatology, Yamaguchi University Graduate School of Medicine

• Takami Taro

  Department of Liver Regenerative Medicine, Yamaguchi University Graduate School of Medicine Center for Regenerative and Cell Therapy, Yamaguchi University Organization for Research Initiatives

• Fujisawa Koichi

  Department of Liver Regenerative Medicine, Yamaguchi University Graduate School of Medicine

• Matsumoto Toshihiko

  Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine

• Yamamoto Naoki

  Health Administration Center, Yamaguchi University

• Sakaida Isao

  Department of Gastroenterology & Hepatology, Yamaguchi University Graduate School of Medicine Center for Regenerative and Cell Therapy, Yamaguchi University Organization for Research Initiatives

抄録

Mesenchymal stem cells, which have the potential to be used in regenerative medicine, require improvements in quality for patient use. To maintain stemness of cultured bone marrow-derived mesenchymal stem cells, we focused on the bone marrow microenvironment, generated a conditioned medium of whole bone marrow cells (BMC-CM), and assessed its effects on bone marrow-derived mesenchymal stem cells. BMC-CM suppressed morphological deterioration and proliferative decline in cultured bone marrow-derived mesenchymal stem cells, suppressed mitochondrial oxidative phosphorylation activity, a stemness indicator, and upregulated suppressors of oxidative phosphorylation such as hypoxia-inducible factor-1 alpha, Sirtuin 3, 4, and 5. Furthermore, BMC-CM upregulated TNF-stimulated gene 6 and ameliorated the therapeutic effects of cells on liver injury in carbon tetrachloride-administered rats. Since the elimination of 20–220-nm particles attenuated the effects of BMC-CM, we further analyzed exosomal microRNAs produced by whole bone marrow cells. Among the 49 microRNAs observed to be upregulated during the preparation of BMC-CM, several were identified that were associated with suppression of oxidative phosphorylation, upregulation of TNF-stimulated gene 6, and the pathogenesis of liver diseases. Thus, bone marrow-derived humoral factors including exosomal microRNAs may help to improve the therapeutic quality of bone marrow-derived mesenchymal stem cells for liver regenerative therapy.

収録刊行物

• Ｊｏｕｒｎａｌ　ｏｆ　Ｃｌｉｎｉｃａｌ　Ｂｉｏｃｈｅｍｉｓｔｒｙ　ａｎｄ　Ｎｕｔｒｉｔｉｏｎ

  Ｊｏｕｒｎａｌ　ｏｆ　Ｃｌｉｎｉｃａｌ　Ｂｉｏｃｈｅｍｉｓｔｒｙ　ａｎｄ　Ｎｕｔｒｉｔｉｏｎ 66 (3), 213-223, 2020

  一般社団法人　日本酸化ストレス学会

キーワード

• mesenchymal stem cell
• oxidative phosphorylation
• TNF-stimulated gene 6
• microRNA
• liver disease

詳細情報

• CRID: 1390003825178873344
• NII論文ID: 130007839286
• DOI: 10.3164/jcbn.19-125
• ISSN: 18805086
• ISSN: 09120009
• Web Site: https://www.jstage.jst.go.jp/article/jcbn/66/3/66_19-125/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2021069166
• 本文言語コード: en
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