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A step toward producing organs from iPS cells

The Yomiuri Shimbun

By Akira Fuyuki / Yomiuri Shimbun Staff WriterJapanese researchers have accelerated studies using induced pluripotent stem (iPS) cells in the hope of creating human organs inside animal bodies, with a series of findings reported since last year that could mark a step toward realizing the technology. The advancements have heightened expectations among patients in need of organ transplants.

There are about 13,000 people in Japan with serious heart, kidney and other organ diseases who are awaiting transplants. However, only about 300 of them receive transplants per year.

To improve the situation, a research team led by University of Tokyo Prof. Hiromitsu Nakauchi, 65, devised new technology for creating organs using iPS cells, which can develop into any type of cell. In 2010, the team successfully created a rat pancreas in a mouse.

Chimera (see below) animals possess cells from different genes. The technology involves injecting a rat iPS cell into an embryo grown from a mouse’s fertilized egg, which is then put back into the mouse’s womb. The resulting baby mouse contains cells derived from the rat.

The study used a mouse embryo genetically modified so that it could not produce a pancreas. The research team was able to deduct that the organ was reproduced through the rat cells; otherwise, a mouse without a pancreas would have been born.

Applying this technology could make it possible to create human organs inside the bodies of animals such as pigs.

In January, the Salk Institute for Biological Studies in the United States and other groups announced that their scientists had inserted human iPS cells into pig embryos and successfully created pig fetuses containing human cells. The institute said this marked “the first step toward the generation of transplantable human organs using large animals.”

This has put the U.S. scientists one step ahead of their Japanese counterparts.

In the same month, the team at the University of Tokyo announced that it had created a pancreas derived from a mouse in a rat’s body. The pancreatic cells were then transplanted into a diabetic mouse, whose diabetes was later confirmed to have been successfully treated. The implanted mouse stayed in good health over a long period, with very few doses of immune suppressor needed.

“We proved our method to be effective and safe. We’re planning to start producing human organs within five years, and hope to deliver them to patients,” Nakauchi said.

Putting an embryo containing human cells into an animal womb is prohibited in Japan due to ethical reasons. Nakauchi will move his base to a U.S. lab to create a human-sheep chimera.

A woman in her 40s from Chiba Prefecture has been suffering from inextirpable Type 1 diabetes since she was 1 year old. Two years ago, her eldest son, who is in kindergarten, was also diagnosed with the disease.

“[People with this disease] have to keep injecting insulin for their entire lives using syringes or other means,” she said. “I hope technology to produce organs for patients, including my son, is realized as soon as possible.”

Success rate still low

The U.S. scientists aim to develop a new technology that would serve as an “organ factory.” However, it was not easy task to create their human-pig chimera.

The team used more than 40 staff members to insert 1,466 embryos into pig wombs over four years. However, only 67 of the resultant pig fetuses contained human cells, and the ratio of human cells to pig cells was low — one cell or less per 100,000.

An expert said this is probably due to the huge difference between the human and pig species. Technical improvements may be necessary to grow organs large enough to transplant.

The Education, Culture, Sports, Science and Technology Ministry is discussing lifting the ban on chimeras created using human and other animal cells.

“Research in Western countries is expected to advance significantly, and all the crucial findings could be taken by researchers overseas if the current situation continues,” Nakauchi said.

■ Chimera

Animals, organs or parts in which cells from two genetically different organisms coexist. Grafting in plants is an example. The word comes from a Greek mythological creature that has a lion’s head, a goat’s body and a snake’s tail.

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