PITTSBURGH, Jan. 23 /PRNewswire/ -- Carnegie Mellon University scientist Chien Ho and colleagues have developed a promising tool that uses magnetic resonance imaging (MRI) to track immune cells as they infiltrate a transplanted heart in the early stages of organ rejection. This pre-clinical advance, published online in the Proceedings of the National Academy of Sciences (PNAS) on Jan. 23, could provide a non-invasive way to detect transplant rejection.
(Logo: http://www.newscom.com/cgi-bin/prnh/20020422/CMULOGO)
“We report for the first time the ability to monitor single immune cells in a live animal using MRI. This could revolutionize the management of transplant patients,” said Ho, biological sciences professor.
“Successful translation of this work to the clinic ultimately will reduce the number of biopsy procedures and should greatly improve the quality of life for cardiac transplant patients, especially children.” Ho directs the Pittsburgh NMR Center for Biomedical Research. “Most importantly, this advance will allow doctors to provide highly personalized care that could prevent transplant rejection.”
Organ transplantation is the preferred approach to treat end-stage organ failure, but transplant patients risk losing the new organ due to rejection. Physicians typically monitor patients for rejection following a heart transplant by performing frequent heart biopsies the first year. Heart biopsies are invasive and involve threading a catheter through the jugular vein to the heart’s right ventricle and snipping out several fragments of tissue. A pathologist then tests the tissue to identify immune cells (such as macrophages) and other pathological changes in transplanted heart tissue that indicate graft rejection.
These procedures are costly, uncomfortable and needed for a few years to monitor and treat rejection. They also are problematic for other reasons, states Ho. Because they sample only several small areas, biopsies may miss an area of the graft where immune cells gather -- one of the first signs of rejection.
Ho’s novel approach investigates transplant rejection non-invasively by observing macrophage accumulation in heart tissues using MRI.
“We used MRI to visualize individual macrophages. By tracking single cells, we also were able to observe, for the first time, that rejection progresses from the outside of the heart to the inside,” said Ho. “Up to now, this phenomenon hasn’t been observed in pre-clinical or clinical research because biopsy samples are very limited in location and size.”
The findings also have broader implications for biology and medicine, stated Ho.
“We now can visualize non-invasively and with sensitivity individual cells and their movement to targeted sites. Our new approach offers almost unlimited potential for monitoring cell therapies, such as those using stem cells, and for tracking cellular and developmental processes,” Ho said.
For the research reported in PNAS, Yijen Wu, research biologist at the Pittsburgh NMR Center, tagged macrophages with nanometer (USPIO)- or micrometer (MPIO)-sized paramagnetic iron oxide particles, which are very sensitive to magnetic fields used during MRI. Wu injected MPIO or USPIO particles into rats that had received heart transplants three days earlier. Macrophages, which typically ingest foreign materials inside the body (bacteria, for example), incorporated the particles. Using MRI, the researchers then track tagged macrophages that infiltrate transplanted hearts. This finding indicates that the new, real-time tracking method is very good at pinpointing exactly when and where rejection is occurring.
Ho’s team is pursuing research using larger animal models with University of Pittsburgh School of Medicine collaborators.
The research is funded by the National Institutes of Health and the Pennsylvania Commonwealth. A research image is available by contacting 412-268-7761.
Carnegie Mellon University
Photo: NewsCom: http://www.newscom.com/cgi-bin/prnh/20020422/CMULOGOAP Archive: http://photoarchive.ap.orgPRN Photo Desk, photodesk@prnewswire.com
CONTACT: Lauren Ward, +1-412-268-7761, or Amy Pavlak, +1-412-268-8619,both of Carnegie Mellon University
Web site: http://www.cmu.edu/
