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On July 9, local time, NYU Langone Health in New York announced the death of Lisa Pisano, the second patient globally to receive a gene-edited pig kidney transplant. This patient was also the first case of a combined transplant involving a mechanical heart and a genetically engineered pig kidney.
Currently, both pig heart and kidney transplant patients worldwide have been reported deceased, and investigations into the second pig kidney transplant patient are ongoing.
Previously, 47 days after the transplant, Lisa Pisano’s kidney function declined due to insufficient blood flow caused by the left ventricular assist device (LVAD). Doctors were compelled to remove the transplanted kidney.
Chen Zhonghua, Chief Advisor of Organ Procurement at Tongji Hospital in China, stated in an interview, "The patient's death 40 days after kidney removal and resuming dialysis was expected." He noted that the patient had pre-existing heart and kidney failure. Kidney failure is a contraindication for heart transplantation, while heart failure is a contraindication for kidney transplantation. As a result, she was one of only four xenotransplant patients approved under compassionate use by the U.S. Food and Drug Administration (FDA).
Chen speculated that the causes of death could be attributed to the following factors:
1. Heart Failure: The patient's heart failure could not provide stable blood circulation, and although she underwent mechanical heart surgery, it still could not adequately support the blood supply required for the transplanted pig kidney.
2. Long-term Dialysis: The patient had been on dialysis for years due to kidney failure. After receiving the gene-edited pig kidney transplant, significant ischemic damage occurred, leading to the removal of the kidney and the continuation of dialysis for life support.
3. Immunosuppressive Therapy: The strong immunosuppressive regimen would have impacted the patient's immune system's normal function and caused drug-related damage to other organs.
4. Xenogeneic Antigen Response: The introduction of foreign antigens may have triggered a substantial inflammatory response within the patient’s body. The simultaneous administration of potent immunosuppressants, alongside the activation of the immune system by the implanted organ, created a complex "immune emergency state."
In the future, scientists plan to analyze this case in depth to establish more precise selection criteria for the next round of clinical explorations in xenogeneic organ transplantation, improving treatment methods and management strategies.
Previously, journals such as The Lancet, Nature Medicine, and Cell have published articles addressing the early immune responses associated with xenogeneic organ transplantation from various omics and single-cell perspectives.
Chen emphasized, "Currently, research on the immediate hyperacute rejection in xenotransplantation has made progress measured in minutes, hours, and days; however, studies on progressive rejection mechanisms and prevention strategies measured in weeks, months, and years have only just begun."
As of now, there have been no subsequent reports on patients who received gene-edited pig liver transplants, which may be due to the fact that liver transplants occurred only in May. We hope to see healthy recipients in the coming months.
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