Nano(bio)Materials Do Not Affect Macrophage Phenotype-A Study Conducted by the REFINE Project

Area of Science:

• Biomedical Engineering
• Nanotoxicology
• Immunology

Background:

• Macrophages play a crucial role in the biocompatibility and biodistribution of nano(bio)materials.
• Rodent cell lines may not accurately reflect human cellular responses to nanomaterials.
• Isolating human tissue-resident macrophages is challenging, limiting in vitro studies.

Purpose of the Study:

• To develop and validate a standard operating procedure (SOP) for differentiating human monocytes into macrophages.
• To assess the utility of this human monocyte-derived macrophage (hMDM) model for studying nano(bio)material interactions.
• To investigate the secretion of bioactive molecules from M1 and M2 differentiated hMDMs in response to model nano(bio)materials.

Main Methods:

• Developed a standard operating procedure (SOP) for differentiating primary human monocytes into M1 and M2 macrophages.
• Assessed pyrogenic contamination to ensure reliable results.
• Measured the secretion of bioactive molecules from differentiated macrophages exposed to model nano(bio)materials.
• Validated the SOP across two independent research institutions.

Main Results:

• The developed SOP for hMDM differentiation was successfully implemented and yielded broadly similar results across institutions.
• The assay demonstrated the utility of hMDMs for studying nano(bio)material interactions.
• Significant donor variability was observed in macrophage responses to nano(bio)materials, reflecting in vivo heterogeneity.

Conclusions:

• The SOP provides a valuable tool for studying nano(bio)material interactions using human-derived macrophages.
• Donor variability, while a challenge, makes this model more physiologically relevant than non-human cell lines.
• This approach is crucial for advancing the regulatory science of nano(bio)material-based medical products.