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

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.