Biological activity reduction and mitochondrial and lysosomal dysfunction of mesenchymal stem cells aging in vitro

作者：Ge Zhang, Yuli Wang, Jianhua Lin, Bo Wang, Ali Mohsin, Zhimin Cheng, Weijie Hao, Wei‐Qiang Gao, Huiming Xu, Meijin Guo · 发表于：Stem Cell Research & Therapy · 年份：2022 · DOI：10.1186/s13287-022-03107-4 · 被引用次数：16 · 研究领域：Mesenchymal stem cell research、Autophagy in Disease and Therapy、Pluripotent Stem Cells Research

BACKGROUND: Mesenchymal stem cells (MSCs) have been extensively used for the treatment of various diseases in preclinical and clinical trials. In vitro propagation is needed to attain enough cells for clinical use. However, cell aging and viability reduction caused by long-time culture have not been thoroughly investigated, especially for the function of mitochondria and lysosomes. Therefore, this study was designed to detect mitochondrial and lysosomal activity, morphological and functional changes in human umbilical cord MSCs (UMSCs) after long-time culture. METHODS: First, we examined cell activities, including proliferation and immigration ability, differentiation potential, and immunosuppressive capacity of UMSCs at an early and late passages as P4 (named UMSC-P4) and P9 (named UMSC-P9), respectively. Then, we compared the mitochondrial morphology of UMSC-P4 and UMSC-P9 using the electronic microscope and MitoTracker Red dyes. Furthermore, we investigated mitochondrial function, including mitochondrial membrane potential, antioxidative ability, apoptosis, and ferroptosis detected by respective probe. Cell energy metabolism was tested by mass spectrometry. In addition, we compared the lysosomal morphology of UMSC-P4 and UMSC-P9 by electronic microscope and lysoTracker Red dyes. Finally, the transcriptome sequence was performed to analyze the total gene expression of these cells. RESULTS: It was found that UMSC-P9 exhibited a reduced biological activity and showed an impai...