The delivery of hsa-miR-11401 by extracellular vesicles can relieve doxorubicin-induced mesenchymal stem cell apoptosis

  • Stem Cell Res Ther. 2021 Jan 22;12(1):77. doi: 10.1186/s13287-021-02156-5.
Huifang Li  1  2 ,  Haoyan Huang  1 ,  Xiaoniao Chen  3 ,  Shang Chen  1 ,  Lu Yu  1 ,  Chen Wang  1 ,  Yue Liu  1 ,  Kaiyue Zhang  1 ,  Lingling Wu  4 ,  Zhong-Chao Han  5  6  7 ,  Na Liu  8 ,  Jie Wu  9 ,  Zongjin Li  10  11
Affiliations
  • 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. [email protected].
  • 9. State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, 100853, China. [email protected].
  • 10. Nankai University School of Medicine, Tianjin, China. [email protected].
  • 11. The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, the College of Life Sciences, Tianjin, China. [email protected].
PMID: 33482923 DOI: 10.1186/s13287-021-02156-5
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.

Keywords
Doxorubicin; Extracellular vesicles (EVs); Hsa-miR-11401; Mesenchymal stem cells (MSCs).
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