Chimeras for Xenotransplantation

Progress in decellularization is one of the reasons that xenotransplantation of animal organs into people may become a going concern. Decellularization is the chemical removal of cells from a donor organ, leaving behind the intricate structure of the extracellular matrix and chemical cues that instruct cells how to populate the organ; there have been some successes in past years in using decellularization to form and transplant comparatively simple structures, such as tracheas. It should be possible to take a pig's heart, strip out the of all pig cells, and repopulate it with a human recipient's cells; porcine and human organs are similar enough that the use of pigs as an organ source has been considered for some time. Adding decellularization to the technology platform may provide a way to establish a low-cost source of donor organs on demand that will arrive prior to the ability to grow entire complex organs from a patient's own cells.

Another possible approach is outlined in a recent Signals post, which is to grow actual human organs in animals:

Hiromitsu Nakauchi has a vision for regenerative medicine. In this vision, he sees a renewable source of human organs for transplantation that are grown within the bodies of farm animals. Here's how it works: pluripotent stem cells would be injected into an early animal embryo that is not capable of generating a specific organ. As the animal embryo develops, the human pluripotent cells would differentiate into the missing organ. This human organ would then be removed and transplanted into a patient.


In 2010, Nakauchi published a report in Cell describing the generation of a rat pancreas in a mouse ... Normal rat pluripotent stem cells were injected into a mouse embryo in which a key gene involved in pancreas development had been deleted (leaving the mouse incapable of forming a pancreas) and indeed rat pluripotent stem cells were able to generate a functioning rat pancreas in the mouse.

This month in the American Journal of Pathology, Nakauchi's group published the generation of kidney from induced pluripotent stem cells in a mouse lacking a key kidney developmental gene using the same technology.

At the ISSCR meeting earlier this month in Yokohama, Japan, Nakauchi described his work translating this technology to large farm animals. Using two transgenic pig lines, normal, fluorescent orange pig pluripotent stem cells were injected into a pancreas incompetent pig embryo. The result: a chimeric pig with a fluorescent orange pancreas.

In Japan (and many other countries), pluripotent stem cells cannot legally be injected into another embryo for the generation of chimeras, thus the long-term goal of generating interspecies chimeras between human and pig could not be tested. Nakauchi told the audience that he would need collaborators from other countries to perform these experiments.

This seems like a promising line of work, though it remains to be seen how well it competes with the evident enthusiasm in the research community for direct construction of new organs from a patient's cells. One might suspect that is one of those applications of science that is doomed to be tied up in knee-jerk politics and regulation, however, attacked by people who have few objections to farming gene-engineered animals for meat as soon as it starts to make any headway.


I would prefer it if there were an open discussion about the possibility of accidentally creating an animal that is actually half-human, half-animal. Science is moving forward very quickly. It would be much better to draw a line before someone accidentally crosses it.

Posted by: Rielly Stares at January 2nd, 2013 8:59 AM
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