New MPI technology can map where therapeutic cells go in the body

A new study in mice shows that an advanced imaging technique called magnetic particle imaging, or MPI, can track exactly where therapeutic cells go after they are injected into the body. This approach could eventually help researchers and doctors study and optimize cell-based therapies for people with multiple sclerosis (MS).

Using MPI, investigators found that mesenchymal stem cells move differently through the body in a mouse model of MS than in healthy mice. Mesenchymal stem cells are a specific cell type with immune-modulating properties that are currently being studied as a potential treatment strategy for MS.

“Using MPI, we can visualize where therapeutic cells end up in the body,” Jeff Bulte, PhD, lead author of the study at the Johns Hopkins University School of Medicine, said in a university news story. “Our research suggests MPI is a promising avenue for helping determine a more precise dose of cell therapy for individual patients.”

The study, “Whole-body in vivo MPI cytometry reveals injection route-, dose-, cell size–, and disease-dependent differences in organ distribution,” was published in Science Advances.

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The hurdle of tracking cell therapies

Cell therapies are a rapidly advancing field of biological technology in which living cells are injected into a person’s body to fight disease. In MS, there’s been a lot of research focused on mesenchymal stem cells (MSCs), immature cells that can differentiate into fat and connective tissue and also secrete signaling molecules that can reduce inflammation.

Although cell therapies have shown promise for MS and other diseases, a major obstacle to their use is that, once injected into the body, it has not been possible for researchers and clinicians to track where the cells actually go. MPI aims to solve that problem.

Very simply, MPI works by labeling therapeutic cells with magnetically-charged nanoparticles, then using a specialized scanner to track the movement of the magnetic particles — and, by extension, the cells themselves.

In their study, the researchers conducted a battery of proof-of-concept tests using MPI to track the movement of two different types of stem cells in healthy mice. The cell types included MSCs and another type of stem cell, neural progenitor cells, which are notably smaller than MSCs.

“Selecting these large and small cells can help us compare the effect of cell size and delivery route for cell therapy treatments,” said Ali Shakeri-Zadeh, PhD, first author of the study at Johns Hopkins.

The researchers found that the movement of cells through the body differs slightly depending on cell size and whether they are injected into arteries (which carry oxygen-rich blood away from the heart to the body’s organs) or veins (which carry blood back to the heart). Broadly, though, results showed that cells injected into the bloodstream tend to accumulate in two organs: the lungs and the liver.

In addition to tests using healthy mice, the researchers also used MPI to track MSC movement in mice with experimental autoimmune encephalomyelitis (EAE), a lab-induced immune condition commonly used to model MS.

“We selected [human] MSCs for these experiments because they are among the most widely used therapeutic cell types in preclinical and clinical MS studies and are known to exert potent immunomodulatory effects,” the scientists wrote.

Results showed that MSCs in EAE mice tended to accumulate in the liver and lungs, similar to what was seen in healthy mice. However, unlike in healthy mice, MSCs in the mouse model also accumulated in the spleen, an organ that plays important roles in regulating immune function.

The accumulation of MSCs in the spleen of mice with EAE is consistent with the idea that these stem cells may help modulate the activity of inflammation-driving immune cells in MS, the researchers said. Using MPI to track these cells’ movements “may open the door to correlating splenic stem cell load with disease severity, [immune activity], and therapeutic outcomes,” they wrote.

“In autoimmune diseases, particularly MS, it’s thought that harmful immune cells … are released from the spleen,” said 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.”