From Pig to Patient: How Columbia Researchers Are Bringing Xenotransplantation Closer to Reality

After decades of research, scientists at the Columbia Center for Translational Immunology are making bold strides toward clinical xenotransplantation—transplanting organs from genetically modified pigs into humans. Megan Sykes, MD, Director of the Columbia Center for Translational Immunology, explains how her team’s breakthroughs in immune tolerance are paving the way for this once-unthinkable future.

What is xenotransplantation—and why is it important?

The basic idea of xenotransplantation is to use organs from another species—most often pigs—to transplant into humans. It’s a solution to a critical and growing problem: there simply aren’t enough human donor organs to meet the need. We’ve lost too many patients who couldn’t get a transplant in time.

Pigs are a good match biologically in terms of organ size and function, and they breed quickly. But there’s a huge immunological barrier—because pigs are so evolutionarily distant from humans, their organs are immediately rejected by the human immune system. That’s where our work on immune tolerance comes in.

How is Columbia uniquely equipped to tackle this challenge?

Columbia has a unique combination of clinical expertise, translational research infrastructure, and collaboration between teams. Within the Columbia Center for Translational Immunology (CCTI), we’ve spent years building models that help us study how to teach the immune system to accept a pig organ instead of attacking it.

We’ve developed small animal models, including humanized mice—mice without immune systems that we reconstitute with human immune systems—and used them to test strategies for inducing tolerance to pig tissue. From those, we’ve progressed to large animal models—preclinical studies using genetically modified pigs and non-human primates.

We’re also lucky to have a unique herd of inbred miniature swine. These pigs are more similar in size to humans than standard pigs, and we’ve engineered them genetically in ways that make them more suitable as donors. Being inbred also means we can standardize and repeat experiments in ways that simply wouldn’t be possible otherwise.

You mentioned “tolerance”—what does that mean in this context?

Tolerance means the recipient’s immune system accepts the transplanted organ as part of the body—without the need for lifelong immunosuppressive drugs. This is the “holy grail” of transplant immunology.

In xenotransplantation, tolerance is even more critical because rejection happens faster and more aggressively. We've developed two major strategies to induce tolerance: one involves transplanting a pig thymus gland alongside the organ so the recipient’s T cells learn to see the pig as “self.” Another involves mixed chimerism—creating a state where both the donor and recipient’s immune cells coexist in the bone marrow.

Both strategies have shown success in our models, including long-term pig kidney survival in non-human primates. And excitingly, these findings are now informing early-stage trials at other institutions, including pig-to-human transplants.

What does clinical xenotransplantation look like in the near future?

We’re optimistic. Our goal is to bring pediatric heart xenotransplantation into the clinic within five years. It’s a critical need. Infants and young children can wait months for a heart transplant, and many don’t survive the wait. If we can safely transplant a heart from a genetically engineered pig, that could be life-saving.

We’ve recently received funding from the American Heart Association to support this work, and the collaboration between our immunology team and Columbia’s pediatric heart surgeons is key. We’re already seeing success in animal models, and we’re laying the groundwork for regulatory and ethical frameworks to move this into human trials.

Why is Columbia the place for this kind of research?

There’s an unusually strong partnership here between researchers and clinicians. Our surgeon-scientists don’t just do operations—they’re part of the lab meetings. We hold joint seminars, we mentor trainees together, and we’re all committed to moving the science into the clinic.

That culture has allowed us to grow this work over decades. It’s deeply collaborative, and that’s what it takes to tackle a challenge as complex as xenotransplantation.

What’s most exciting to you right now?

For me, it’s the idea that decades of work are finally paying off. We’re seeing tolerance strategies that really work. We’ve got the right models. We have the infrastructure. And we’re finally seeing real-world applications emerge. This is no longer science fiction—it’s science that’s ready to serve patients.