Huifang Li1,2, Haoyan Huang1, Xiaoniao Chen3, Shang Chen1, Lu Yu1, Chen Wang1, Yue Liu1, Kaiyue Zhang1, Lingling Wu4, Zhong-Chao Han5,6,7, Na Liu8, Jie Wu9, Zongjin Li10,11. 1. Nankai University School of Medicine, Tianjin, China. 2. The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, the College of Life Sciences, Tianjin, China. 3. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. 4. State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, 100853, China. 5. Jiangxi Engineering Research Center for Stem Cell, Shangrao, Jiangxi, China. 6. Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, National Engineering Research Center of Cell Products, AmCellGene Co., Ltd., Tianjin, China. 7. Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co, Beijing, China. 8. Nankai University School of Medicine, Tianjin, China. liuna@nankai.edu.cn. 9. State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, 100853, China. wujie301@126.com. 10. Nankai University School of Medicine, Tianjin, China. zongjinli@nankai.edu.cn. 11. The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, the College of Life Sciences, Tianjin, China. zongjinli@nankai.edu.cn.
Abstract
BACKGROUND: Chemotherapy is an effective anti-tumor treatment. Mesenchymal stem cells (MSCs), exerting therapy effect on injured tissues during chemotherapy, may be damaged in the process. The possibility of self-healing through long-range paracrine and the mechanisms are unclear. METHODS: Doxorubicin, a commonly used chemotherapy drug, was to treat human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) for 6 h as an in vitro cell model of chemotherapy-induced damage. Then we use extracellular vesicles derived from placental mesenchymal stem cells (hP-MSCs) to investigate the therapeutic potential of MSCs-EVs for chemotherapy injury. The mechanism was explored using microRNA sequencing. RESULTS: MSC-derived extracellular vesicles significantly alleviated the chemotherapy-induced apoptosis. Using microRNA sequencing, we identified hsa-miR-11401, which was downregulated in the Dox group but upregulated in the EV group. The upregulation of hsa-miR-11401 reduced the expression of SCOTIN, thereby inhibiting p53-dependent cell apoptosis. CONCLUSIONS: Hsa-miR-11401 expressed by MSCs can be transported to chemotherapy-damaged cells by EVs, reducing the high expression of SCOTIN in damaged cells, thereby inhibiting SCOTIN-mediated apoptosis.
BACKGROUND: Chemotherapy is an effective anti-tumor treatment. Mesenchymal stem cells (MSCs), exerting therapy effect on injured tissues during chemotherapy, may be damaged in the process. The possibility of self-healing through long-range paracrine and the mechanisms are unclear. METHODS:Doxorubicin, a commonly used chemotherapy drug, was to treat human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) for 6 h as an in vitro cell model of chemotherapy-induced damage. Then we use extracellular vesicles derived from placental mesenchymal stem cells (hP-MSCs) to investigate the therapeutic potential of MSCs-EVs for chemotherapy injury. The mechanism was explored using microRNA sequencing. RESULTS:MSC-derived extracellular vesicles significantly alleviated the chemotherapy-induced apoptosis. Using microRNA sequencing, we identified hsa-miR-11401, which was downregulated in the Dox group but upregulated in the EV group. The upregulation of hsa-miR-11401 reduced the expression of SCOTIN, thereby inhibiting p53-dependent cell apoptosis. CONCLUSIONS:Hsa-miR-11401 expressed by MSCs can be transported to chemotherapy-damaged cells by EVs, reducing the high expression of SCOTIN in damaged cells, thereby inhibiting SCOTIN-mediated apoptosis.
Authors: Alfonso Varela-López; Maurizio Battino; María D Navarro-Hortal; Francesca Giampieri; Tamara Y Forbes-Hernández; José M Romero-Márquez; Ricardo Collado; José L Quiles Journal: Food Chem Toxicol Date: 2019-09-29 Impact factor: 6.023
Authors: Anouk E Hiensch; Kate A Bolam; Sara Mijwel; Jeroen A L Jeneson; Alwin D R Huitema; Onno Kranenburg; Elsken van der Wall; Helene Rundqvist; Yvönne Wengstrom; Anne M May Journal: Acta Physiol (Oxf) Date: 2019-10-31 Impact factor: 6.311