1. Academic Validation
  2. The delivery of hsa-miR-11401 by extracellular vesicles can relieve doxorubicin-induced mesenchymal stem cell apoptosis

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

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. 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.

Keywords

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

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