Ca2+-activated mitochondrial biogenesis and functions improve stem cell fate in Rg3-treated human mesenchymal stem cells

Stem Cell Research & Therapy

Young Woo Eom¹  Su Jung Park²  Moon Young Kim³  Soon Koo Baik³  Kyu-Sang Park⁴  Dat Da Ly⁴  Taeui Hong⁵ 

[1] Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Ilsan-ro 20, 26426, Wonju, Gangwon-Do, Republic of Korea;Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, 26426, Wonju, Gangwon-Do, Republic of Korea;Mitohormesis Research Center, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, 26426, Wonju, Gangwon-Do, Republic of Korea;Department of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, 26426, Wonju, Gangwon-Do, Republic of Korea;Mitohormesis Research Center, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, 26426, Wonju, Gangwon-Do, Republic of Korea;Department of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, 26426, Wonju, Gangwon-Do, Republic of Korea;Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Ilsan-ro 20, 26426, Wonju, Gangwon-Do, Republic of Korea;Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, 26426, Wonju, Gangwon-Do, Republic of Korea;Mitohormesis Research Center, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, 26426, Wonju, Gangwon-Do, Republic of Korea;Department of Physiology, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, 26426, Wonju, Gangwon-Do, Republic of Korea;Mitohormesis Research Center, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, 26426, Wonju, Gangwon-Do, Republic of Korea;Department of Physiology, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, 26426, Wonju, Gangwon-Do, Republic of Korea;Department of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, 26426, Wonju, Gangwon-Do, Republic of Korea;

关键词: Mesenchymal stem cells;    Ginsenoside Rg3;    Cellular senescence;    Oxidative stress;    Mitochondria;   

DOI  :  10.1186/s13287-020-01974-3

来源: Springer

【 摘 要 】

Although mitochondrial functions are essential for cell survival, their critical roles in stem cell fate, including proliferation, differentiation, and senescence, remain elusive. Ginsenoside Rg3 exhibits various biological activities and reportedly increases mitochondrial biogenesis and respiration. Herein, we observed that Rg3 increased proliferation and suppressed senescence of human bone marrow-derived mesenchymal stem cells. Osteogenic, but not adipogenic, differentiation was facilitated by Rg3 treatment. Rg3 suppressed reactive oxygen species production and upregulated mitochondrial biogenesis and antioxidant enzymes, including superoxide dismutase. Consistently, Rg3 strongly augmented basal and ATP synthesis-linked respiration with high spare respiratory capacity. Rg3 treatment elevated cytosolic Ca2+ concentration contributing to mitochondrial activation. Reduction of intracellular or extracellular Ca2+ levels strongly inhibited Rg3-induced activation of mitochondrial respiration and biogenesis. Taken together, Rg3 enhances capabilities of mitochondrial and antioxidant functions mainly through a Ca2+-dependent pathway, which improves the proliferation and differentiation potentials and prevents the senescence of human mesenchymal stem cells.

【 授权许可】

CC BY