Organ transplantation is a significant medical breakthrough, but it still faces challenges such as rejection by the immune system. Transplant recipients often need to take immune-suppressing medication for life, leading to risks and side effects. However, Evan Scott, a new biomedical engineering professor at the University of Virginia, is pioneering research to help the body accept transplanted organs without compromising the immune system. His work involves using nanoparticles to make transplanted organ cells resistant to immune system attacks, potentially eliminating the need for lifelong immunosuppressive drugs.
Scott, who recently joined UVA after 11 years at Northwestern University, co-authored a study published in Proceedings of the National Academy of Science. The study focused on modifying immune responses in a controlled way to reduce the need for immunosuppressive drugs in transplant patients. Beyond organ transplants, Scott’s research could have implications for addressing immune rejection in other areas such as diabetes, cell therapy, and autoimmune disorders. He will also lead UVA’s Institute for Nanoscale Scientific and Technological Advanced Research (NanoSTAR) as part of the new Paul and Diane Manning Institute of Biotechnology.
Existing treatments for organ rejection either suppress the immune system or build tolerance to help the body accept the new organ. Scott’s lab focuses on retraining the immune system to tolerate new cells, aiming to rewire cellular-level instructions that trigger immune attacks on transplanted organs. One key focus of the research is targeting myeloid cells, particularly monocytes that can transform into inflammatory macrophages to combat intruders. By targeting a protein called HIF-2α, Scott and his team were able to signal to the immune system that transplanted heart cells should not be attacked, leading to better acceptance of transplanted organs in mice.
The therapeutic strategy involves using nanoparticles encapsulating the drug Roxadustat to increase the levels of HIF-2α in monocytes, which are targeted in the spleen. By modifying circulating white blood cells, the therapy aims to prevent the transformation of monocytes into inflammatory macrophages and signal the immune system to leave transplanted heart cells alone. This approach was successful in improving the acceptance of transplanted hearts in mice. Scott emphasizes the potential of this strategy to treat various disorders by modifying how circulating monocytes respond to their environment, showing promise for a wide range of therapeutic applications.
Overall, Scott’s innovative work with nanoparticles represents forward-thinking science that could reshape medical fields by addressing immune rejection in organ transplantation and other areas. Dean of the School of Engineering Jennifer L. West praises Scott’s contributions and welcomes him to the UVA community. By focusing on retraining the immune system and targeting specific cellular processes, Scott’s research offers a promising solution to the challenges of organ rejection and the need for immune-suppressive medication in transplant recipients. His continued research at UVA’s NanoSTAR could lead to further advancements in treating immune-related disorders and improving patient outcomes.