Franken-Swine: World’s First Pig-to-Human Lung Transplantation

For those suffering from end-stage respiratory failure, lung transplantation is often a necessary life-saving procedure. Various lung problems can result in the need for transplantation, the most common of which is chronic obstructive pulmonary disease (COPD), a condition caused by inflammation and damage in the lungs that leads to difficulty breathing and frequent chest infections. COPD accounts for 40% of all lung transplants globally (Kumar et al. 2024).

Despite the urgent need for lung transplantations for many patients, the procedure is limited due to a major issue: the shortage of appropriate organs. NHS Blood and Transplant recently revealed that, as of March 2025, there were 8,096 patients on the active transplant waiting list in the UK, the highest number recorded to date. Additionally, in 2024/2025, 4,583 individuals received organ transplants, which was 2% less than the previous year. 

This highlights the disheartening reality that the organ shortage crisis is continuing to grow.

Fortunately, scientists have come up with a plan B — xenotransplantation, the act of transplanting live tissue from one species to another.

In this blog, we discuss the realities of pig-to-human lung transplantation.

Designer Pigs

While the concept may seem like something straight from science fiction, xenotransplantation is, in fact, much more logical than you may think. Pigs, in particular, have the potential to provide viable organs for humans, as their organ size, immune system, and physiological metabolism are remarkably similar to humans (Xi et al. 2023).

However, a major problem exists in the form of rejection. Rejection occurs when the immune system of the host recognizes the grafted organ as foreign and mounts an immune response against it.

Rejection can be subclassified into different types: hyperacute, acute, and chronic rejection, categorized by how quickly the patient’s immune system reacts. Different mechanisms can mediate rejection, hence the further subclassification into antibody-mediated rejection (AMR) and T cell–mediated rejection (TCMR).

TCMR is the most common type of rejection, in which, as the name suggests, the host’s T cells recognize and subsequently attack the antigens of the donor, and is identified by the detection of mononuclear cell infiltration in a graft biopsy.

AMR, however, is the most destructive form of rejection (Chancharoenthana et al. 2023). Antibodies against antigens on the donor organ, either preexisting in the host body or produced via the activation of B cells, are deposited within the graft and, once bound, can provoke the activation of the complement system. This triggers a cascade of enzyme activation, which ultimately leads to inflammatory responses such as the activation of phagocytes, production of cytokines, and cell lysis. C4d, a component of the complement system, is often used as a marker for AMR (Cohen et al. 2012).

So, what have scientists come up with to overcome this hurdle?

Fortunately, pigs can be genetically modified to reduce recognition and attack by the immune system. Using genetically engineered pigs as donors has significantly advanced xenotransplantation, leading to groundbreaking cases of pig-to-human heart and kidney transplants (Xi et al. 2023).

And now, scientists have progressed another step with the world’s first human-to-pig lung transplant (He et al. 2025).

A Breath of Fresh Air

In this pioneering study, He et al. utilized a lung from a pig with six genetic modifications: three genes encoding cell surface sugars on the pig cells that provoke strong immune responses in humans (GGTA1, CMAH, and B4GALNT2) were removed, and three human genes encoding proteins that regulate the immune response (hCD46, hCD55, and hTBM) were inserted.   

The modified organ was transplanted into a 39 year old brain-dead human recipient, who was administered a concoction of immunosuppressants, including the antibody drugs rituximab and eculizumab and the fusion protein belatacept, to further halt the activation of the immune response.

Scientists then closely monitored the status of the xenotransplant.

The organ managed to circumvent the usual issues of hyperacute rejection and early graft failure, remaining functional and viable for nine days without evidence of severe systemic inflammation.

Unfortunately, however, increased levels of proinflammatory cytokines and macrophages indicated an early localized inflammatory response, and pulmonary edema was observed.

Additionally, despite the genetic edits made to the graft and the immunosuppressant regimen given to the recipient, a robust humoral response was evident, reflecting the rapid onset of AMR.

The scientists terminated the experiment on day 9 post-operation upon request by the recipient’s family.  

While the experiment lasted little over a week and critical issues were observed, this procedure represents a profound scientific advancement and uncovers crucial insights into lung xenotransplantation. He et al. remain hopeful of the promising findings, stating the need for optimization through further genetic modifications and additional strategies for lung preservation.

This marks a step closer to clinical translation of pig-to-human lung transplantation.