CMU scientist develops technique to detect transplant rejection

Organ transplant rejection, particularly of the heart, is a major obstacle to successful transplantation today. There were 2016 heart transplants performed in the United States in 2004, and 2057 in 2000, according to the American Heart Association. With this many people needing heart transplants, it is important to prevent these foreign organs from being rejected by the host person’s immune system.

What if there were a way to detect heart transplant rejection before it happened? The results of the surgery could be predicted, and the number of failed transplants would decrease greatly.

In Chien Ho’s laboratory at the Pittsburgh Nuclear Magnetic Resonance (NMR) Center for Biomedical Research, great discoveries have been made in detecting organ rejection before it occurs in the patient. This noninvasive approach involves labeling immune cells, mainly macrophages, with iron oxide particles, which are easily traced by magnetic resonance imaging (MRI). The labeled macrophages can be found around rejection sites.

When last-stage organ failure occurs, the organ is so damaged that it can no longer be repaired, and the only treatment is transplantation. Organ transplantation faces many challenges, including organ rejections and a shortage of donor organs, which is why it would be very advantageous to detect rejection of transplanted organs before it happens.

The procedures taken to reduce risk of rejection following transplants are costly, unpleasant, and repetitive. Immunosuppressive therapy involves injecting the patient with cyclosporin, an agent used to reduce the body’s natural immune defenses. This prevents the patient’s immune system from attacking and destroying the foreign organ. Cyclosporin must be used carefully; too much cyclosporin can be dangerous, since it is a very strong drug, but too little of the drug can result in organ rejection.

Heart biopsy, performed during the first year after the transplant, is a diagnostic procedure in which a catheter is inserted through a vein or artery to one of the ventricles of the heart. Three to five small pieces of tissue are removed from the heart muscle and examined by pathologists to determine whether immune cells are present, indicating potential rejection. This invasive procedure can produce inaccurate results because the biopsies only focus on the area where tissue was removed rather than the whole organ. The area where rejection is occurring could be missed completely. Ho’s noninvasive procedure can avoid this pitfall, since it is capable of using MRI to detect the labeled immune cells’ location throughout the entire heart.

“We are very excited about our MRI detection of cardiac rejection in our rodent model. We hope that our noninvasive approach to detect organ rejection will be applied to humans after additional research,” Ho said.

Ho’s research involved transplanting a functional heart into a rat’s abdomen and observing the effects. Ho and his team studied how the transplanted heart changed through the stages of rejection while the rat was still healthy. Immune cells injected three days prior to the transplantation were labeled with a contrasting agent containting iron oxide. High-contrast spots on an MRI scan indicated accumulations of immune cells attacking the foreign tissue.

This research has received funding from institutions including the National Heart, Lung, and Blood Institute; the National Institute of Biomedical Imaging and Bioengineering; the Health Research Formula Funds of the Pennsylvania Commonwealth University Research Enhancement Tobacco Settlement; and the National Center for Research Resources.

Ho and his team plan to continue their study with larger animals. Since their approach is very new, much testing must still be done before this procedure can be performed on humans. But when the lives of thousands of transplant patients are at stake, it’s all worth it.