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Effects of Adenoviral Gene Transduction on the Stemness of Human Bone Marrow Mesenchymal Stem Cells

机译:腺病毒基因转导对人骨髓间充质干细胞干性的影响

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摘要

Human mesenchymal stem cells (MSCs) are currently being evaluated as a cell-based therapy for tissue injury and degenerative diseases. Recently, several methods have been suggested to further enhance the therapeutic functions of MSCs, including genetic modifications with tissue- and/or disease-specific genes.The objective of this study was to examine the efficiency and stability of transduction using an adenoviral vector in human MSCs. Additionally, we aimed to assess the effects of transduction on the proliferation and multipotency of MSCs. The results indicate that MSCs can be transduced by adenoviruses in vitro, but high viral titers are necessary to achieve high efficiency. In addition, transduction at a higher multiplicity of infection (MOI) was associated with attenuated proliferation and senescence-like morphology. Furthermore, transduced MSCs showed a diminished capacity for adipogenic differentiation while retaining their potential to differentiate into osteocytes and chondrocytes. This work could contribute significantly to clinical trials of MSCs modified with therapeutic genes.
机译:人间充质干细胞(MSCs)目前正在评估为基于细胞的组织损伤和退行性疾病疗法。最近,已经提出了几种方法来进一步增强MSC的治疗功能,包括用组织和/或疾病特异性基因进行遗传修饰。这项研究的目的是检验在人体内使用腺病毒载体进行转导的效率和稳定性。 MSC。此外,我们旨在评估转导对MSC增殖和多能性的影响。结果表明,腺病毒可在体外转导MSC,但高病毒滴度是获得高效率所必需的。另外,以更高的感染复数(MOI)进行的转导与增殖减弱和衰老样形态相关。此外,转导的MSC显示出成脂分化能力降低,同时保留了其分化为骨细胞和软骨细胞的潜力。这项工作可以极大地促进治疗基因修饰的MSC的临床试验。

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