Highlights

Researchers at TGen, the Phoenix-based nonprofit biomedical research institute that is part of City of Hope, published findings Monday showing that heart transplant rejection involves molecular changes far more complex than what standard biopsy imaging captures, a result that could eventually help clinicians predict which patients will respond to anti-rejection therapies.

The study, published in Nature Cardiovascular Research, used spatial transcriptomics to map gene expression at the subcellular level across a series of cardiac tissue biopsies from 62 adult and child heart transplant patients. Every transplant patient is biopsied regularly to monitor for rejection, but until now those samples have been evaluated primarily through histology.

Of the more than 4,500 cardiac transplants performed annually in the U.S., up to 35% experience rejection within a year of their procedure. The two main rejection types are acute cellular rejection, in which a patient's T cells attack the heart, and antibody-mediated rejection, driven by antibodies. Both can contribute to long-term transplant failure and death by predisposing patients to chronic rejection conditions including cardiac allograft vasculopathy.

The TGen and Vanderbilt Health team found broad overlap in gene expression states across different levels of rejection severity, and even differences in expression patterns within the same rejection severity grade, a finding that challenges the assumption that histology grades reliably predict outcomes.

"A lot of information just can't be captured by image data alone. Having this extra layer of molecular information adds a new tool for determining outcomes," said Nicholas Banovich, Ph.D., professor and director of the Division of Bioinnovation and Genome Sciences at TGen and a senior author of the study. "This doesn't replace a pathologist's expertise in evaluating tissue samples and determining what's happening. Instead, it provides additional insights that can support prognosis and help guide treatment decisions."

Kaushik Amancherla, M.D., assistant professor of medicine at Vanderbilt Health and co-first author, noted that considerable heterogeneity from one biopsy sample to another makes consistent interpretation a challenge under current methods. Angela Taravella Oill, Ph.D., a TGen computational scientist and co-lead author, said the team was able to identify and map the spatial organization of immune and cardiac cell types involved in rejection.

When the team examined baseline rejection biopsies, patients who responded to immune-modulating anti-rejection drugs had gene expression profiles different from those who did not, a finding the researchers described as among the most significant in the study. The work was also corroborated by coverage from Vanderbilt Health News and EurekAlert.

Why does this matter for transplant outcomes?

Patients with the same biopsy-based rejection severity grade can have very different clinical outcomes. The TGen-led study found that gene expression patterns vary even within the same grade, suggesting molecular profiling could one day support more precise treatment decisions for the roughly 1,575 U.S. transplant patients who experience rejection each year.

The study did not disclose commercialization timelines, funding sources, or licensing arrangements. TGen's next publication schedule was not announced.

Sources

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  1. tgen.org retrieved 11/08/2026 03:45

Authored by The Scottsdale Signal. Drafted by AI from primary-source material under our beat-specific editorial guides; reviewed by humans before publish under our five-gate process. Sources retrieved at 11/08/2026 03:45. Every claim traces to a source.