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Researchers at a biotech company co-founded by a medical student from Hawaii have taken human fetal kidneys that would have been discarded and transplanted them into rats, where they thrived.
Their ultimate goal is to grow such organs in animals and make them available to children and adults who need lifesaving transplants but can’t get them because of the shortage of donated organs.
"The big dream for us is really about being able to take these organs and put them back into humans," said Nick K. Chang, who was born and raised in Honolulu and is a medical student at Duke University as well as CEO of Ganogen Inc. of Redwood City, Calif.
There are hurdles ahead before that dream can be realized, involving risks of rejection, infection and ethical questions. But in the short run, the researchers believe their work opens a new frontier for testing drugs on human organs within a living animal host, without putting human subjects at risk.
"What makes us stand far apart from previous attempts is this is the first time we had a whole human kidney transplanted into a rat," said Eugene Gu, who is also a Ganogen CEO and medical student at Duke. "It’s always been a theoretical possibility, but to watch it actually grow was pretty amazing."
123,000
Approximate number of people in the U.S. who need organ transplants, mostly kidneys
14,000
The number of organ donors in 2013
U.S. Department of Health and Human Services
Their research is chronicled in an article in the Jan. 22 issue of the American Journal of Transplantation, "Arterial Flow Regulator Enables Transplantation and Growth of Human Fetal Kidneys in Rats."
"Previously, people transplanted parts of a kidney or kidney tissues into a rat or very immature embryonic stem cells into a rat, but never actually a full kidney that can function, and never anything that could support the life of the animal," Gu said.
Chang, 31, and Gu, 28, are Stanford graduates who launched Ganogen in 2012. They conceived and carried out the experiment, with help from Ganogen colleagues Jay Gu and Suphain Gu, and guidance from Dr. Robert W. Osorio, chairman of California Pacific Medical Center’s Department of Transplantation, and Dr. Waldo Concepcion, a professor of surgery at Stanford University Medical Center. All six are co-authors of the study.
The privately funded experiment used fetal organs made available for medical research that otherwise would have been discarded after abortions. The fetal kidneys, about 17 weeks’ gestation, were transplanted into adult rats whose immune systems had been suppressed.
The transplants required microscopic surgery, performed by Eugene Gu, with stitches several times smaller than the width of a human hair.
"What’s impressive is the technical part — their ability to operate and successfully implant such a small organ, sewing such small blood vessels," said Dr. Whitney Limm, a transplant surgeon at the Queen’s Medical Center in Honolulu, who specializes in kidneys and read the study. "As far as applications in the future, I think there is much work to be done."
Adult rats have much higher blood pressure than human fetuses. To get around that problem, the team invented a saline-filled cuff, an "arterial flow regulator," to adjust blood pressure and flow into the human kidney.
Gradually, blood flow was increased until it reached full force after 30 days. At that point the rat’s original kidneys were removed, letting the transplanted organ take over kidney function.
"To our knowledge, no group has been able to transplant fetal organs into adult animal hosts due to the inherent mismatch between fetal and adult blood pressures," the researchers wrote in their journal article.
The rats with the new kidneys lived for about four months after their transplant. Rats used as controls whose kidneys were removed without a replacement transplant lived for three days.
The kidneys weighed about 0.6 grams when they were transplanted, and more than quadrupled in weight and volume in 45 days.
"These findings suggest that human fetal kidneys discarded after therapeutic abortion procedures remain viable, which may have immediate implications for fatal in utero diseases," the researchers wrote. "For example, fetal-to-fetal renal transplantation may be possible in humans without the need for animal intermediaries."
"In addition, the ability to transplant human fetal kidneys within animal models may have great utility for in vivo (in the body, versus test tube) pharmaceutical drug testing and discovery."
Ganogen intends to transplant other fetal organs, such as livers and hearts, into rats and work on kidney transplants in larger animals, such as pigs, in their effort to ramp up and eventually produce donor organs.
"We really feel like this is providing a gateway for a lot of people to getting actual cures for their ailments," said Chang, who graduated from Punahou in 2002 and is pursuing a Stanford law degree concurrently with his medical studies at Duke.
More than 123,000 people in the United States need an organ transplant, mostly kidneys, according to the U.S. Department of Health and Human Services. The number of donors falls far short, at about 14,000 donors in 2013.
The fetal kidneys used by Ganogen came from Stem Express, a Placerville, Calif., company that supplies biomedical researchers with human tissue and clinical specimens. Stem Express had obtained Institutional Review Board approval and consent from patients who donated the fetal organs for research.
Asked about the ethics of their work, Gu said fetal tissue has long been used in research, including development of the polio vaccine, and that corporations have used embryonic kidney cell lines, which are easy to manipulate genetically, to test flavor enhancers.
"These human fetal tissues are used very routinely in both science and industry," Gu said. "We think that it is a lot more ethical to use human fetal tissues to directly save the lives of a human patient, a child or a baby on the transplant waiting list than it is to use it for a commercial purpose."
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