Cells, especially immune cells, need oxygen to function, but too little or too much can be harmful. The chair group of Cell biology and immunology of Wageningen University & Research will investigate the role of oxygen carriers in the immune response. "Our SPICE project, short for super-charged immune cells, will study the role of special oxygen carriers in the cell: perfluorocarbons. We will test if these particles can support cells with low-oxygen environments, like tumours or areas with infections", explains professor Mangala Srinivas. The SPICE project is supported by a NWO-M grant.
Perfluorocarbons (PFCs) are developed as artificial oxygen carriers in clinical settings. In the last decade, nanoparticles were designed incorporating PFCs, originally as a stable agent for MRI-based in-vivo cell tracking. Researchers at the chair group of Cell biology and immunology (CBI) want to investigate if these PFC-rich imaging agents can create internally oxygen-supplemented cells (IOSCs). For this research, the chair group applied for and was awarded an NWO-M grant. With the M-grants, the Dutch NOW board supports innovative, high-quality, fundamental research and/or studies involving matters of scientific urgency.
Ultimate goal
"Our ultimate goal is to create super-charged immune cells (SPICE) that can improve treatments for various health conditions", states Srinivas. IOSCs could, according to the WUR professor, potentially carry oxygen to oxygen-deprived environments, such as solid tumours, sites of arthritis, or drug-resistant bacterial biofilms, all the while avoiding the harmful production of reactive oxygen species. "However, there is a substantial knowledge gap when it comes to safely loading cells with adequate oxygen and maintaining their oxygen levels long enough to make a meaningful impact."
Enhance performance
The CBI research aims to study and enhance the performance of immune cells loaded with oxygen-rich PFC NPs in low-oxygen environments. The researcher will employ techniques commonly used in other research domains, such as respirometry, cell-based assays, 3D cell culture, soft X-ray tomography, and imaging, along with standard assays to measure intracellular hypoxia-inducible factor levels (HIFs) in immune IOSCs. "We will assess how these oxygen-loaded immune cells behave in a 3D migration model, and with tumour spheroids. Our overarching goal is to investigate the effects of oxygen loading to generate highly efficient immune cells, which we term 'super-charged immune cells' or 'SPICE'."
Insights
According to Srinivas, SPICE has the potential to provide groundbreaking insights into the impact of intracellular oxygen and its role in modulating the immune response. "The implications of this research extend beyond cancer, encompassing areas including stem cell transplants, reperfusion therapies, and combating infections - areas that suffer from hypoxia in vivo." The SPICE project started on February 1 and will run for four years. First results of the research is expected in the course of 2025.
