Adriana Smith, a 30-year-old woman from Georgia who had been declared brain-dead in February 2025, spent 16 weeks on life support while doctors worked to keep her body functioning well enough to support her developing fetus. On June 13, 2025, her premature baby, named Chance, was born via cesarean section[1] at 25 weeks.
Smith was nine weeks pregnant when she suffered multiple blood clots in her brain. Her story gained...
A pioneering study has provided unprecedented insights into the immune response following pig-to-human kidney xenotransplantation.1
The findings, presented today at the ESOT Congress 2025, mark a significant step forward in overcoming the biggest challenge in xenotransplantation: rejection by the human immune system.
Using cutting-edge spatial molecular imaging, researchers mapped how human immune cells interact with pig kidney tissue in transplanted organs, revealing critical early markers of rejection and potential intervention strategies. The study, led by Dr. Valentin Goutaudier and a collaborative international research team (Paris Institute for Transplantation and Organ Regeneration & NYU Langone Transplant Institute), highlights key molecular mechanisms that could shape the future of xenotransplantation.
One of the most striking discoveries was that human immune cells were found in every part of the pig kidney's filtering system after the transplant. Researchers observed early molecular signs of antibody-mediated rejection as soon as Day 10 and peaking at Day 33, reinforcing previous findings that rejection begins rapidly but progresses over time.2 By tracking these immune responses for up to 61 days, the team identified a crucial window for targeted therapeutic intervention.
"Our study provides the most detailed molecular map to date of how the human immune system engages with a transplanted pig kidney," explained Dr. Goutaudier. "By pinpointing specific immune cell behaviours and gene expressions, we can refine anti-rejection treatments and improve transplant viability."
The study's innovative approach used a bioinformatic pipeline to distinguish human immune cells from pig structural cells, allowing for precise mapping of immune infiltration patterns. Notably, macrophages and myeloid cells were the most prevalent immune cell types across all time points, further confirming their role as key mediators in xenograft rejection.
When targeted therapeutic interventions were introduced, immune-mediated signs of rejection were successfully weakened. Combined with novel spatial insights into how immune cells interact with pig kidney tissue, this marks a major breakthrough -- paving the way for more refined anti-rejection strategies. These advances come at a pivotal time as the first US-based clinical trials of pig kidney transplantation into living human recipients begin in 2025.
With xenotransplantation poised to address the global organ shortage crisis, these findings bring researchers one step closer to making genetically modified pig kidneys a viable long-term solution. The next phase will focus on optimising anti-rejection treatments, refining genetic modifications in donor pigs, and developing early detection protocols to monitor and manage rejection responses.
"Understanding the specific immune interactions at a molecular level allows us to develop targeted interventions that can prevent rejection before it escalates," explained Dr. Goutaudier. "This research lays the groundwork for safer and more effective pig-to-human transplants in the near future."
As scientific progress accelerates, researchers remain cautiously optimistic that genetically modified pig kidneys could become a routine transplant option within the next decade. However, regulatory approvals will require consistent demonstration of safety and efficacy in diverse patient populations.
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New research from the University of Pittsburgh School of Medicine and La Jolla Institute for Immunology, published today (June 30) in Nature Microbiology, reveals an opportunity for developing a therapy against cytomegalovirus (CMV), the leading infectious cause of birth defects in the United States.
Researchers discovered a previously unappreciated mechanism by which CMV, a herpes virus that infects the majority of the world's adult population, enters cells that line the blood vessels and contributes to vascular disease. In addition to using molecular machinery that is shared by all herpes viruses, CMV employs another molecular "key" that allows the virus to sneak through a side door and evade the body's natural immune defenses.
The finding might explain why efforts to develop prophylactic treatments against CMV have, so far, been unsuccessful. This research also highlights a new potential avenue for the development of future antiviral drugs and suggests that other viruses of the herpes family, such as Epstein-Barr and chickenpox, could use similar molecular structures to spread from one infected cell to the next while avoiding immune detection.
"If we don't know what weapons the enemy is using, it is hard to protect against it," said senior author Jeremy Kamil, Ph.D., associate professor of microbiology and molecular genetics at Pitt. "We found a missing puzzle piece that represents one possible reason why immunization efforts against CMV have been unsuccessful."
In the United States, approximately one in every 200 babies is born with congenital CMV infection. Of the babies infected, one in five will have birth defects, such as hearing loss, or go on to have long-term health challenges. For most adults, CMV infections are asymptomatic. But a CMV infection during pregnancy presents significant health risks to the unborn child and could be deadly for people who are immunosuppressed, including organ transplant recipients.
Because of the large size of its genome and its complicated molecular machinery, CMV long evaded attempts to develop prophylactic treatments. Similar to other herpes viruses, CMV relies on a protein called gH to enter cells of the vessel lining. But unlike other herpes viruses, which use a protein partner called gL to facilitate infection, the new study found that CMV replaces gL with another partner called UL116 and recruits a protein called UL141. The resulting complex of gH-UL116-UL141, called GATE by the authors, then becomes an alternative tool for breaking into cells lining the blood vessels and causing internal damage while simultaneously preventing the body's own immune system from recognizing the signs of infection.
The newly discovered GATE could become a potential vaccine target for CMV and other herpes viruses.
"Previous attempts to generate a CMV vaccine have failed, but that was before we identified the GATE complex. We hope that new strategies targeting GATE will improve our chances to combat CMV infection, and also perhaps cleanse our bodies of this lifelong infection," said Chris Benedict, Ph.D., associate professor at La Jolla Institute for Immunology and co-senior author of the study with Kamil and LJI professor, president & CEO Erica Ollmann Saphire, Ph.D., MBA. "If we can develop antiviral drugs or vaccines that inhibit CMV entry, this will allow us to combat the many diseases this virus causes in developing babies and immune-compromised people."
Other authors of this research are Michael Norris, Ph.D., of the University of Toronto; Lauren Henderson, Mohammed Siddiquey, Ph.D., both of Louisiana State University Health Shreveport; and Jieyun Yin, Ph.D., Kwangsun Yoo, Ph.D., Simon Brunel, Ph.D., Michael Mor, Ph.D., and Erica Ollmann Saphire, Ph.D., all of La Jolla Institute for Immunology.
This research was supported by the National Institutes of Health (grants AI11685, AI139749, AI101423 and T32HL155022) and by ARPA-H APECx contract 1AY1AX000055.