Platelet-Derived Mitochondria Attenuate 5-FU-Induced Injury to Bone-Associated Mesenchymal Stem Cells

作者：Yutong Chen, Yutong Chen, Zhixin Liu, Ning An, Jing Zhang, Weicheng Meng, Wenting Wang, Xiaoshuang Wu, Xingbin Hu, Yaozhen Chen, Yaozhen Chen, Wen Yin · 发表于：Stem Cells International · 年份：2023 · DOI：10.1155/2023/7482546 · 被引用次数：13 · 研究领域：Oral health in cancer treatment、Mitochondrial Function and Pathology、Cancer, Hypoxia, and Metabolism

Background. Myelosuppression is a common condition during chemotherapy. Bone-associated mesenchymal stem cells (BA-MSCs) play an essential role in the composition of the hematopoietic microenvironment and support hematopoietic activity. However, chemotherapy-induced damage to BA-MSCs is rarely studied. Recent studies have shown that platelets promote the wound-healing capability of MSCs by mitochondrial transfer. Therefore, this study is aimed at investigating the chemotherapy-induced damage to BA-MSCs and the therapeutic effect of platelet-derived mitochondria. Material/Methods. We established in vivo and in vitro BA-MSC chemotherapy injury models using the chemotherapy agent 5-fluorouracil (5-FU). Changes in the mitochondrial dynamics were detected by transmission electron microscopy, and the expression of mitochondrial fusion and fission genes was analyzed by qRT-PCR. In addition, mitochondrial functions were also explored by flow cytometry and luminometer. Platelet-derived mitochondria were incubated with 5-FU-damaged BA-MSCs to repair the injury, and BA-MSC functional changes were examined to assess the therapy efficacy. The mechanism of treatment was explored by studying the expression of mitochondrial fission and fusion genes and hematopoietic regulatory factor genes in BA-MSCs. Results. Stimulation with 5-FU increased the apoptosis and suppressed cell cycle progression of BA-MSCs both in vivo and in vitro. In addition, 5-FU chemotherapy inhibited the hematopoietic reg...