期刊
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
卷 132, 期 3, 页码 310-320出版社
SOC BIOSCIENCE BIOENGINEERING JAPAN
DOI: 10.1016/j.jbiosc.2021.05.010
关键词
Mesenchymal stem cell; Actin cytoskeleton; Mitochondrial function; Cytochalasin B; Microfluidics; Oxygen sensor
资金
- No Forschungsund Bildungsges.m.b.H. [FthornB LS15-004]
- government of Lower Austria, Department of Economics, Tourism and Technology (WST3) [WST3-F-5030664/009-2018]
- European Regional Development Fund [INTERREG ATCZ 133, 215]
- Austrian Center for Medical Innovation and Technology (ACMIT Gmbh) Nikolaus Dellantoni
This study demonstrates a causal connection between mitochondrial function and the cytoskeleton, showing that damage to the filamentous actin-based cytoskeleton can efficiently recover the mitochondrial function of MSCs.
Owing to their self-renewal and multi-lineage differentiation capability, mesenchymal stem cells (MSCs) hold enormous potential in regenerative medicine. A prerequisite for a successful MSC therapy is the rigorous investigation of their function after in vitro cultivation. Damages introduced to mitochondria during cultivation adversely affect MSCs function and can determine their fate. While it has been shown that microtubules and vimentin intermediate filaments are important for mitochondrial dynamics and active mitochondrial transport within the cytoplasm of MSCs, the role of filamentous actin in this process has not been fully understood yet. To gain a deeper understanding of the interdependence between mitochondrial function and the cytoskeleton, we applied cytochalasin B to disturb the filamentous actin-based cytoskeleton of MSCs. In this study we combined conventional functional assays with a state-of-the-art oxygen sensor-integrated microfluidic device to investigate mitochondrial function. We demonstrated that cytochalasin B treatment at a dose of 16 mu M led to a decrease in cell viability with high mitochondrial membrane potential, increased oxygen consumption rate, disturbed fusion and fission balance, nuclear extrusion and perinuclear accumulation of mitochondria. Treatment of MSCs for 48 h ultimately led to nuclear fragmentation, and activation of the intrinsic pathway of apoptotic cell death. Importantly, we could show that mitochondrial function of MSCs can efficiently recover from the damage to the filamentous actin-based cytoskeleton over a period of 24 h. As a result of our study, a causative connection between the filamentous actin-based cytoskeleton and mitochondrial dynamics was demonstrated. (C) 2021, The Society for Biotechnology, Japan. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据