Abstract
BackgroundChemotherapy 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.MethodsDoxorubicin, 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.ResultsMSC-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.ConclusionsHsa-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.
Highlights
Cell culture The human placental mesenchymal stem cells and human umbilical cord-derived mesenchymal stem cells used in this study were from the preserved cells in our lab, which were isolated from the same source as that used in a previous study [14]
Previous studies revealed that the apoptosis of targeted cell treated with doxorubicin was related to its intracellular accumulation [17], which can be visualized through fluorescent signal of doxorubicin
The mesenchymal stem cells may be injured by the nonspecific mechanism and KOBAS based on the discrepancy of miRNA in Dox and Extracellular vesicles (EVs) groups, which are related to the therapeutic potential of hP-Mesenchymal stem cells (MSCs)-derived extracellular vesicles for doxorubicin cytotoxicity. c The binding sites and match diagram between hsa-miR-11401 and SCOTIN are presented, and the expression of hsa-miR-11401 and SCOTIN among groups was further verified
Summary
Mesenchymal stem cells (MSCs), exerting therapy effect on injured tissues during chemotherapy, may be damaged in the process. Its therapeutic effects can be achieved by replacing damaged cells or by its paracrine. Some researchers have found that MSCs can alleviate cell apoptosis, and that can be used to treat doxorubicin-induced cytotoxicity in basic researches [10, 11]. These findings indicated that mesenchymal stem cells may play an important role to alleviate chemotherapy injury. MSCs may be damaged in this process and its therapy effects may be abolished. How MSCs respond to chemotherapeutic agents and the fate of MSCs during chemotherapy are not clear
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