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非细胞毒性石墨烯纳米片上调间充质干细胞的细胞增殖和自我更新基因。

Non-Cytotoxic Graphene Nanoplatelets Upregulate Cell Proliferation and Self-Renewal Genes of Mesenchymal Stem Cells.

机构信息

Cell Therapy Laboratory (LATEC), University of Caxias do Sul (UCS), Caxias do Sul 95070-560, Brazil.

Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre 90610-000, Brazil.

出版信息

Int J Mol Sci. 2024 Sep 11;25(18):9817. doi: 10.3390/ijms25189817.

Abstract

Graphene nanoplatelets (UGZ-1004) are emerging as a promising biomaterial in regenerative medicine. This study comprehensively evaluates UGZ-1004, focusing on its physical properties, cytotoxicity, intracellular interactions, and, notably, its effects on mesenchymal stem cells (MSCs). UGZ-1004 was characterized by lateral dimensions and layer counts consistent with ISO standards and demonstrated a high carbon purity of 0.08%. Cytotoxicity assessments revealed that UGZ-1004 is non-toxic to various cell lines, including 3T3 fibroblasts, VERO kidney epithelial cells, BV-2 microglia, and MSCs, in accordance with ISO 10993-5:2020/2023 guidelines. The study focused on MSCs and revealed that UGZ-1004 supports their gene expression alterations related to self-renewal and proliferation. MSCs exposed to UGZ-1004 maintained their characteristic surface markers. Importantly, UGZ-1004 promoted significant upregulation of genes crucial for cell cycle regulation and DNA repair, such as CDK1, CDK2, and MDM2. This gene expression profile suggests that UGZ-1004 can enhance MSC self-renewal capabilities, ensuring robust cellular function and longevity. Moreover, UGZ-1004 exposure led to the downregulation of genes associated with tumor development, including CCND1 and TFDP1, mitigating potential tumorigenic risks. These findings underscore the potential of UGZ-1004 to not only bolster MSC proliferation but also enhance their self-renewal processes, which are critical for effective regenerative therapies. The study highlights the need for continued research into the long-term impacts of graphene nanoplatelets and their application in MSC-based regenerative medicine.

摘要

石墨烯纳米片(UGZ-1004)作为一种有前途的再生医学生物材料正在兴起。本研究全面评估了 UGZ-1004,重点关注其物理特性、细胞毒性、细胞内相互作用,特别是对间充质干细胞(MSCs)的影响。UGZ-1004 的横向尺寸和层数与 ISO 标准一致,表现出 0.08%的高碳纯度。细胞毒性评估表明,根据 ISO 10993-5:2020/2023 指南,UGZ-1004 对包括 3T3 成纤维细胞、VERO 肾上皮细胞、BV-2 小胶质细胞和 MSCs 在内的各种细胞系均无毒性。本研究重点关注 MSCs,并揭示 UGZ-1004 支持与自我更新和增殖相关的基因表达改变。暴露于 UGZ-1004 的 MSCs 保持其特征性表面标志物。重要的是,UGZ-1004 促进了细胞周期调控和 DNA 修复关键基因的显著上调,如 CDK1、CDK2 和 MDM2。这种基因表达谱表明,UGZ-1004 可以增强 MSC 的自我更新能力,确保强大的细胞功能和寿命。此外,UGZ-1004 暴露导致与肿瘤发展相关的基因下调,包括 CCND1 和 TFDP1,减轻了潜在的致瘤风险。这些发现强调了 UGZ-1004 不仅可以增强 MSC 的增殖能力,还可以增强其自我更新过程的潜力,这对于有效的再生治疗至关重要。该研究强调了需要对石墨烯纳米片的长期影响及其在基于 MSC 的再生医学中的应用进行持续研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4282/11431873/7a7b4435520e/ijms-25-09817-g001.jpg

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