By Cassie Myers

July 10, 2026

A simple but devastating truth: the only cure for long term organ failure is transplantation. Equally devastating, of course, is the fact that there aren’t enough donated organs available for every person who needs one.

Scientists and physicians have been tackling this problem for decades, approaching from many different angles, including recent attempts to transplant pig organs (with reduced immune activation) into humans. Institute member Hiro Nakauchi, MD, PhD, professor of stem cell genetics, is one such physician-scientist, although his approach may be novel: he hopes to grow more human organs for transplantation, ideally by growing human organs in animals like pigs.

“My major area is hematopoietic stem cells,” he explains, the stem cells present in the bone marrow that can develop into all types of blood cells. His early work convinced him that an empty niche is necessary for successful hematopoietic stem cell transplantation. He then came up with the idea of an organ niche that could be filled by pluripotent stem cells during development through the generation of chimeras (organisms containing cells from two different species).

Earlier experiments showed that you could grow, for example, a rat pancreas in a mouse, and a mouse pancreas in rats. But there were often problems; as Nakauchi explains, cells from different species often failed to survive in their hosts, particularly in a developing embryo. Researchers found that early immune cells, known as primitive macrophages, would attack and engulf the “foreign” cells of the other species in a process they called xenophagocytosis.

“This is quite unique,” Nakauchi explains. “People already knew that macrophages are scavengers – they usually eat dead cells or cell debris. But in this case they’re eating live foreign cells.”

In order to combat this, researchers tried many different approaches and the latest, published recently in Cell, has shown significant promise. Under specific conditions, foreign cells express an “eat-me” signal that triggers the macrophages’ hunger. By blocking this pathway –  either through genetic manipulation or by enhancing signals like CD47 (the well-known “don’t eat me” signal extensively studied at the institute by former ISCBRM director Irv Weissman, MD, current ISCBRM director Ravi Majeti, MD, PhD, and colleagues) – the researchers were able to protect the foreign cells, essentially changing the “eat me” sign the foreign donor cells were giving off to a “don’t eat me,” like a diner neon sign blazing from “open” to “closed.”

This resulted in significant improvement: With this method, “the success rate of generating a rat pancreas in a mouse nearly doubled, increasing from 38% to 73%,” Nakauchi states. These findings may help guide future studies as they attempt to translate this finding into human-pig studies being conducted by their international collaborators.

Moving Forward

Nakauchi has been working on this project (among many others) for over 16 years. “The first author of the first paper, a graduate student at the time, is now a full professor in the National Institute for Physiological Sciences in Japan, so it's been a long time,” he acknowledges. But he believes wholeheartedly that advances such as the one reported in Cell “could be a game changer in organ transplantation medicine.”

He knows this will take a monumental effort, including time and funding and the dedication of countless scientists around the world. But he also believes that it can and should be done. “I’m very optimistic,” he says. “I've done several projects like this in the past. People thought it would never work, but it did. Perhaps that’s why I’m confident that this one can succeed as well.”  

Read more about Hiro Nakauchi's work.