Scientists at Johns Hopkins Medicine say they used a form of magnetic imaging to track cell therapy injections commonly used to treat certain autoimmune diseases and cancers.
The findings, from a study of mice, add to a growing body of evidence that magnetic particle imaging (MPI), a new technique that allows scientists to visualize therapeutic cells as they inject them, may eventually help researchers personalize cell therapy treatments for individual patients. The National Institutes of Health-funded study was published May 6 in Science Advances.
Existing cell therapies include CAR-T cell therapy, in which an individual's immune cells are engineered to seek and destroy cancer cells. The problem with CAR-T cell therapy is that available imaging technology, including conventional MRI and CT scanners, does not allow clinicians to see how many cells are actually delivered and where, and how many of these cells end up targeting a tumor or inflammatory tissues, says corresponding author Jeff Bulte, M.S., Ph.D., professor of radiology and radiological science at the Johns Hopkins University School of Medicine and director of cellular imaging for the Johns Hopkins Institute for Cell Engineering.
"Using MPI, we can visualize where therapeutic cells end up in the body," says Bulte. "Our research suggests MPI is a promising avenue for helping determine a more precise dose of cell therapy for individual patients."
In experiments, the scientists used mesenchymal stem cells (around 25 micrometers), which are commonly studied as a potential avenue for cell therapy to fight autoimmune diseases and cancer in clinical trials, and smaller neural precursor cells (around 10 micrometers) derived from induced pluripotent stem cells.
"Selecting these large and small cells can help us compare the effect of cell size and delivery route for cell therapy treatments," says first author Ali Shakeri-Zadeh, Ph.D., assistant professor of radiology and radiological science and a member of the Institute for Cell Engineering.
By labeling the cells engineered to fight disease, injecting them into normal mice as well as mice with autoimmune encephalomyelitis, then imaging these cells with MPI, Bulte says this technology can potentially help scientists develop more effective treatments for certain cancers, autoimmune diseases including multiple sclerosis (MS), and other neurological conditions such as ALS.
The scientists tagged both cell types with a specialized ultra-tiny nanoparticle, "superparamagnetic iron oxide nanoparticles." Once labeled with these magnetic nanoparticles, the scientists injected the larger mesenchymal stem cells into mice with experimental autoimmune encephalomyelitis (EAE), a commonly used model for studying MS, and into normal mice.
Using MPI, the scientists visualized how many cells were effectively delivered and where they went.
After using MPI to observe the mice, the scientists say injecting the cells into the artery was an effective method of cell therapy delivery, resulting in more cells that were delivered directly to the key target organs to fight disease, including the brain and spleen. The scientists also observed cell accumulation in other organs, including the lungs and liver. The scientists did these same experiments in normal mice, and found that cells similarly traveled to the lungs, liver and brain, but could not be observed at detectable levels in the spleen.
"In autoimmune diseases, particularly MS, it's thought that harmful immune cells, or T cells, are released from the spleen," says Shakeri-Zadeh. "Our experiments in EAE mice, a mouse model of MS, show that therapeutic cells could subdue harmful immune cells right at the source, in the spleen."
The scientists caution that, though cell delivery to the brain through the artery was shown to be effective in terms of accumulating and fighting disease hot spots, the best method to deliver cell therapy may vary from person to person.
In the future, scientists say they intend to broaden these experiments and use MPI to find more effective ways to deliver cell therapy in cancer as well as neurologic diseases.
"If used on a large scale, MPI cytometry has the potential to help personalize treatments for each patient receiving cell therapy treatment," Bulte says.
In addition to Bulte and Shakeri-Zadeh, other scientists who authored the study are Shreyas Kuddannaya, Kritika Sood, Asif Itoo, Cristina Zivko, Aline Thomas and Vasiliki Mahairaki from Johns Hopkins, and Chengyan Chu and Piotr Walczak from University of Maryland.
