Reacción a "First pig-to-human lung transplant performed"

What is your overall impression of the article?

“The article is of high quality, published in Nature Medicine, and rigorously describes the first transplant of a genetically modified pig lung into a brain-dead human. The authors accurately detail both the surgical procedure and the immunological and pathological follow-up, which instils confidence in the robustness of the data.

This is a pioneering, highly relevant and well-executed study. The Guangzhou Medical University (China) group, led by Jianxing He, has an outstanding track record in thoracic surgery, clinical lung transplantation and high-impact scientific production.

The authors provide a detailed account of both the surgical procedure and the very thorough follow-up in four areas (functional, radiological, immunological and pathological), which lends credibility to the data.

How does this fit in with existing evidence and what new information does it provide? What implications could it have?

"The novelty is that this is the first pig lung transplant with six genetic modifications to a brain-dead human. The graft remained viable and functional for 216 hours (nine days) without hyperacute rejection, although there was early oedema and signs of antibody-mediated rejection on days 3–6, with partial recovery on day 9. This is the first human evidence in the lung and confirms the technical feasibility, although challenges remain in terms of oedema, rejection and infection. In addition to previous work on the heart and kidney, a xenotransplantation of a pig liver to a human (heterotopic auxiliary xenotransplantation) in brain death was also recently published (Nature, 2025). In that study, the organ remained functional for 10 days, producing bile and albumin of porcine origin and without immediate rejection.

These studies reinforce that xenotransplantation is entering a clinical experimental phase with reproducible results in several organs, each with specific challenges (e.g., PGD or primary graft dysfunction and particular immunological barriers in the lung; haemodynamics and coagulation in the liver). Both studies used pigs with six modifications (GGTA1, B4GALNT2, CMAH KO + hCD46, hCD55, hTBM), provided by Chengdu Clonorgan Biotechnology, suggesting a convergent genetic platform to minimise hyperacute rejection and endothelial dysfunction.

Are there any important limitations to consider?

"The study has important limitations that should be noted and are explicitly acknowledged by the authors in the article itself. First, the transplant was performed on a brain-dead patient, which means that the results cannot be directly extrapolated to living people, as neither the clinical tolerance nor the actual side effects of the procedure can be assessed. In addition, follow-up was limited to nine days, so we do not know how the graft would evolve in the medium and long term and whether additional complications such as chronic rejection or late infections would appear.

Another key aspect is that the lung presented primary graft dysfunction (PGD) very early on, with severe oedema at 24 hours, which compromised its function from the outset. This was compounded by the appearance of early humoral rejection, with antibody deposits and complement activation from the third day onwards, showing that the immune barrier remains a considerable challenge. It should also be noted that an extremely intensive and complex immunosuppression regimen was used, which is difficult to apply in clinical practice with living patients due to its toxicity and the risk of infections. In this regard, although no serious active infections were detected, traces of latent porcine viruses did appear, indicating that microbiological safety is not yet fully guaranteed.

Finally, this is a single case, which limits the generalisation of the results and requires caution until they are replicated in further studies.