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

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.

Keywords: cell cycle; graphene; mesenchymal stem cells; nanomaterials.

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation* / drug effects
  • Cell Self Renewal / drug effects
  • Cell Self Renewal / genetics
  • Chlorocebus aethiops
  • Gene Expression Regulation / drug effects
  • Graphite* / chemistry
  • Graphite* / pharmacology
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / drug effects
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Nanoparticles / chemistry
  • Nanostructures / chemistry
  • Vero Cells

Substances

  • Graphite

Grants and funding

This research was funded by Coordenacão de Aperfeiҫoamento de Pessoal de Nível Superior (CAPES)—Brazil, Finance Code 001.