It might be possible to transplant embryonic stem cells from pigs into humans to grow new organs, a new study shows.
The idea is not new. For more than two decades, scientists have pointed to the potential of embryonic pig tissues as a source for organ transplantation.
Studies in the past, however, have had little success when tissue has been taken relatively late in a pig embryo's development.
The new study shows that, for the transplantation to be successful, the stem cells need to come from specific stages of an embryo's development.
"By implantation of pig embryonic tissues into immune-deficient mice, we have now determined for the first time distinct gestational time windows for the growth of transplanted pig embryonic liver, pancreas, and lung precursor tissue into functioning tissue," said Yair Reisner, a professor in the Department of Immunology at the Weizmann Institute of Science in Rehovot, Israel.
Using pig tissue to replace failing human organs could help patients with diseases such as diabetes, Parkinson's, and liver failure.
Reisner directed the study, which is reported this week in the U.S. research journal Proceedings of the National Academy of Sciences.
Incompatibility
Researchers say the supply of human organs will always be insufficient to satisfy demands, making xenotransplantation—the act of transplanting organs or tissue between two species—an attractive alternative.
The thought of combining parts from different species goes back to ancient Greece. And as early as 1682 a Russian physician is said to have repaired the skull of a wounded nobleman using bone from a dog. Today faulty human heart valves are routinely replaced with ones taken from cows and pigs.
The major obstacle for xenotransplantation is the immune barrier. The primary cause of organ transplant failure is rejection of the graft organ by the host. In xenotransplantation, the molecular incompatibility between host and donor tissue is greater than it is in human-to-human transplantation.
Embryonic tissues, however, are less likely to provoke an immune response. Still, researchers have not figured out the optimal time to harvest the stem cells in an embryo's development.
"Transplant too early and the risk is [that] embryonic tissue can develop into undesirable and possibly malignant tissue, a type of tumor known as teratoma," Reisner said. "Transplant too late and the risk is that the tissues will have reached the stage where they have been marked with certain identifiers that trigger rejection by the new host."
To identify when to harvest the embryonic cells, the scientists took embryonic pig tissue that had begun to form particular organs at various developmental stages and transplanted them into mice.
They studied three types of organs—liver, pancreas, and lung—and found optimal time windows for transplantation for each organ.
"What he has shown is that there's a window of opportunity," said Bernhard Hering at the Diabetes Institute for Immunology and Transplantation at the University of Minnesota.
"If you obtain this tissue at a very defined point in time, then you can see development into islets [portions of the pancreas that secrete hormones like insulin] without risks such as teratoma formation," Hering said. "That's clearly something that makes us feel very strongly that this could be a real opportunity, one that can be translated into tangible benefits much faster than other technologies."
Reevaluating the Past
The findings could help enhance the chances for successful implementation of embryonic pig tissue in the treatment of a wide spectrum of human diseases, particularly diabetes. The findings may help in part to explain the failure of previous transplantation trials of pancreatic islets in diabetic patients.
"Early studies that attempted to cure diabetic patients by implantation of pig embryonic pancreas made use of late-gestation tissue, which is now shown to be inferior, compared to the optimal six-week gestational time," Reisner said.
Embryonic liver transplants also have a curative potential for enzyme deficiencies and for hemophilia.
The new findings may now allow scientists to go back to their previous work and look at it in a different light.
"Previous failures may have had to do with the timing of the tissue as opposed to it not being able to accomplish appropriate transfer of embryonic tissue to allow it to develop into specific organ type," said Kenneth Chavin, an assistant professor of surgery, microbiology, and immunology at the Medical University of South Carolina in Charleston.