Ouzin Meryem, Wesselborg Sebastian, Fritz Gerhard, Kogler Gesine
Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany.
Institute for Molecular Medicine I, University Hospital, Heinrich Heine University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany.
Cells. 2024 Dec 23;13(24):2134. doi: 10.3390/cells13242134.
The present study investigates the influence of nitrosamines and etoposide on mesenchymal stromal cells (MSCs) in a differentiation state- and biological age-dependent manner. The genotoxic effects of the agents on both neonatal and adult stem cell populations after treatment, before, or during the course of differentiation, and the sensitivity of the different MSC types to different concentrations of MNU or etoposide were assessed. Hereby, the multipotent differentiation capacity of MSCs into osteoblasts, adipocytes, and chondrocytes was analyzed. Our findings reveal that while all cell types exhibit DNA damage upon exposure, neonatal CB-USSCs demonstrate enhanced resistance to genotoxic damage compared with their adult counterparts. Moreover, the osteogenic differentiation of MSCs was more susceptible to genotoxic damage, whereas the adipogenic and chondrogenic differentiation potentials did not show any significant changes upon treatment with genotoxin. Furthermore, we emphasize the cell-specific variability in responses to genotoxic damage and the differences in sensitivity and reaction across different cell types, thus advocating the consideration of these variabilities during drug testing and developmental biological research.
本研究以分化状态和生物学年龄依赖性方式研究亚硝胺和依托泊苷对间充质基质细胞（MSC）的影响。评估了这些药物在分化前、分化过程中或分化后对新生儿和成人干细胞群体的遗传毒性作用，以及不同类型的MSC对不同浓度的N-甲基亚硝基脲（MNU）或依托泊苷的敏感性。据此，分析了MSC向成骨细胞、脂肪细胞和软骨细胞的多能分化能力。我们的研究结果表明，虽然所有细胞类型在暴露后均表现出DNA损伤，但与成体对应细胞相比，新生儿脐带来源的间充质干细胞（CB-USSC）对遗传毒性损伤表现出更强的抗性。此外，MSC的成骨分化对遗传毒性损伤更敏感，而在用基因毒素处理后，其脂肪生成和软骨生成分化潜能未显示任何显著变化。此外，我们强调了细胞对遗传毒性损伤反应的特异性变异性以及不同细胞类型在敏感性和反应方面的差异，因此主张在药物测试和发育生物学研究中考虑这些变异性。
