Researchers at NYU Langone Health have announced successful results from a pair of experimental pig-to-human heart transplant procedures completed on recently deceased human subjects. The volunteers were kept on mechanical ventilation for three days while the organs were monitored in their bodies.
This year is certainly turning into a significant landmark for the field of xenotransplantation. For decades, scientists have been working to solve the organ shortage crisis. One strategy has been to develop genetically modified pigs with organs designed to not be rejected when transplanted into human bodies.
Earlier this year an extraordinary procedure by surgeons at the University of Maryland Medical Center completed the first pig-to-human heart transplant. Through a compassionate use provision from the US Food and Drug Administration (FDA) the pig heart was transplanted into a live human, who subsequently lived for two months before passing away from heart failure.
That xenotransplantation procedure into a live human was an unexpected jump forward for the field. Before that, researchers at NYU Langone were at the front of the pack with their work testing pig organs in recently deceased human subjects.
Last year, the NYU team were the first group in the world to transplant genetically modified pig organs into humans. Across two procedures, surgeons successfully transplanted pig kidneys into recently deceased subjects.
The novel paradigm has been referred to as “whole-body donation,” and it involves volunteers offering their entire body to science for studies that keep them on life-support for several days after brain death. Robert Montgomery, leading the research from the NYU Langone Transplant Institute, says this work is a crucial stepping stone for the field of xenotransplantation, and before this point these organs had only been tested on non-human primates.
“Our greater purpose is to address the organ shortage and provide another option for the more than 100,000 people nationwide waiting on that lifesaving gift,” Montgomery explained. “The paradigm of whole-body donation – when organ donation is not a viable option – is critical to this work moving forward. We are so grateful to the families who volunteer to participate in this research, which will lead to saving untold thousands of more lives.”
The two new procedures were completed over the past six weeks. Both human donors were kept alive on ventilator support for 72 hours after being declared brain dead.
The pig hearts transplanted into the donors had been engineered with 10 specific genetic modifications. Six of those modifications were to include “human transgenes” and four modifications were to knock out certain pig genes that can promote organ rejection.
The protocol for the procedures specifically attempted to follow current clinical heart transplantation standards. So only standard immunosuppressive drugs were used, unlike the Maryland pig-to-human xenotransplant which used certain experimental medications. And standard storage and transportation methods were deployed.
“Our goal is to integrate the practices used in a typical, everyday heart transplant, only with a nonhuman organ that will function normally without additional aid from untested devices or medicines,” said Nader Moazami, surgical director on the project. “We seek to confirm that clinical trials can move ahead using this new supply of organs with the tried-and-true transplant practices we have perfected at the NYU Langone Transplant Institute.”
The experimental procedures were deemed a success, with no signs of rejection as the organs functioned perfectly normally across the 72-hour follow-up. Speaking to CNN Moazami said three days was decided to be the most ethical timeframe to explore the efficacy of these procedures but a lot more work will be needed before this kind of xenotransplantation becomes a clinical reality.
"There's still a long way to go before we go from here to clinical transplantation to support a patient in the longer term," he added. "There's still many, many, many questions that need to be answered."
Source: NYU Langone Health