Megan Strachan, with her dog Ollie, suffers from scleroderma - a rare disease in which the immune system attacks the body. Picture: Norm Oorloff Source: Herald Sun

AS Megan Strachan strolls near her Drouin home, it is difficult to believe that a year ago she was crippled by an incurable disease causing her body to harden and consume itself.

She believes an experimental stem cell transplant has freed up her limbs from the effects of scleroderma - when the immune system attacks victims' skin so it hardens and cannot move.

It can affects joints and lead to organ failure.

The jury is out on whether controversial stem cell treatments can impact the disease that affects up to 5000 Australians, but Ms Strachan is thrilled to have her life back.

"At the time of the transplant I was bedridden. All my joints had contracted, so they were all bent and I couldn't stand up straight because my skin was hard from head to toe," Ms Strachan said.

"Slowly, but surely, over the course of the two years, my skin started softening and I was able to straighten my arms."

Diagnosed just before turning 30, within four months Ms Strachan had to give up her job as a nurse and then moved in with her parents to be looked after.

With no frontline treatment, Ms Strachan talked to an expert in Switzerland, who put her on to haematologist Dr John Moore. He was pioneering autologous stem cell transplants at Sydney's St Vincent's Hospital.

Dr Moore's process involves returning a patient's stem cells in conjunction with chemotherapy, with the toxic drugs responsible for killing off the immune system's attack while stem cells offset the treatment's side-effects.

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Stem cells give woman her life back

Proto-livers in dishes in the lab. Credit: Takanori Takebe

A team of Japanese researchers has created the first functioning human organ, a liver, from induced pluripotent stem cells. While the technology is at least a decade from clinical application, it opens the door to using stem cells to solve the shortage of donor organs.

The organ precursors were grown in the lab using iPS cells. When these early organs, called liver buds, were transplanted into mice, they matured into tissue resembling the adult human liver. After just four to six days, the cells had self-organized into a functioning organ with a healthy blood supply.

The team of researchers at Yokohama City University began with human skin cells, which they genetically reverted to an embryonic stem-cell state and then coaxed into liver-precursor cells. They then exposed these cells to environments similar to what the developing liver experiences in a fetus, adding to the dish stem cells that line blood vessels and form tissues. Within 48 hours the cells had amassed into tiny proto-organs visible to the naked eye.

Once the liver buds were about 4 or 5 millimeters, the team implanted 12 liver buds into either the brain or abdomen of each mousesites chosen for their ease of access. The researchers had labeled the cells with fluorescent proteins, which helped them monitor the buds for formation of blood vessels.

They found that the organ developed a vascular system almost immediately and performed liver-specific functions within weeks. By day ten the transplanted liver buds were producing albumin, a key protein produced by the liver. After 60 days the gene expression of cells in the liver bud had significantly shifted from its precursor cells.

As further proof, the mice were given drugs that mice livers cannot normally metabolize but human livers can. The mice successfully broke down these drugs into the same components that humans do.

The results are published today in Nature.

The technique is unlikely to produce whole replacement livers, but could be used to grow mini-livers that supplement a failing organ. Such transplants wouldnt even need to be located near the existing liver. Lead researcher Takanori Takebe hopes to reduce the size of the liver buds to 100 micrometers, so they can be injected into the bloodstream of mice.

Takebe estimates that with an infusion of hundreds of thousands of liver buds, about 30 percent of a persons liver function could be restored. The limitation at the moment is to create enough suitable liver buds in sufficient quantity to create a viable clinical therapy, he said.

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First Functioning Human Organ Made of Induced Stem Cells

Scientists have for the first time created a functional human liver from stem cells derived from skin and blood - suggesting organs could be grown in labs in another 10 years.

The research could alleviate an acute shortage of donor organs across the world for patients with liver, heart, kidney and other organ failure.

Japanese scientists, based at the Yokohama City University Graduate School of Medicine, said they grew tissue "resembling the (human) adult liver" in a lab mouse.

The team used induced pluripotent stem (iPS) cells, which are often taken from blood and skin, to make three different cell types that would normally combine in the natural formation of a human liver.

These were then mixed to see if they would grow into three-dimensional structures called "liver buds" - the precursor clusters that develop into a full liver organ.

The buds were then transplanted onto a mouse brain, where they were observed transforming into a "functional human liver" complete with blood vessels, the scientists wrote in the journal Nature.

"To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells," said the report.

Takanori Takebe, who led the study, said the liver also performed certain human-specific liver functions - producing proteins and processing specific drugs.

He was so encouraged by the success of this work that he plans similar research on other organs such as the pancreas and lungs.

The technique has yet to be tested in humans, but serves as an important proof of concept, the report added.

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Human Liver Created From Stem Cells In Mouse

There is a shortage of livers available for transplant, meaning thousands die every year (Reuters)

Japanese scientists have grown a fully functional human liver from stem cells for the first time.

The researchers from Yokohama City University created the organ by transplanting 'liver buds' from human stem cells to restore liver function in mice.

Published in the journal Nature, Takanori Takebe and Hideki Taniguchi showed how they stopped mice with liver failure from dying by transplanting the stem cell-grown structures into them.

At present, there is a huge demand for human livers for transplants. In the US last year, almost 3,000 people died waiting for a liver while 5,800 transplants took place.

Embryonic stem cells were discovered in 1981 but scientists have hitherto been unable to generate a human organ because of the complex interactions between cells and tissues as they develop.

However, the Yokohama City scientists challenged this belief by focusing on the earliest stage of organ creation# - the interactions during 'organ bud' development.

There are two main types of stem cells: those that are harvested from embryos, and reprogrammed induced pluripotent stem cells (iPSCs) which are taken from skin and blood.

The researchers used the latter type to make three different cell types that normally combine in the formation of a human liver. They fused them together and found the cells began to grow to form 3D structures called 'liver buds'.

When these were transported into the mice, the liver buds matured and connected with the mouse's blood vessels, and began performing many of the functions of mature human liver cells.

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Human Liver Created From Stem Cells in World First for Japanese Scientists

A mixture of three cell types self-assembles into a liver bud that can be seen with the naked eye.

In work that will raise hope that organs could be repaired or even grown from scratch using a patients own tissue as the raw material, Japanese researchers have created functioning liver tissue from stem cells and successfully transplanted them into mice.

The researchers found that a mixture of human liver precursor cells and two other cell types can spontaneously form three-dimensional structures dubbed liver buds. In the mice, these liver buds formed functional connections with natural blood vessels and perform some liver-specific functions such as breaking down drugs in the bloodstream.

Its possible the technique will work with other organ types, including the pancreas, kidney, or lungs, lead author Takanori Takebe, a scientist at Yokohama City University in Japan, said Tuesday at a press conference, aided by a translator. The study, published in Nature on Wednesday, is the first demonstration that a rudimentary human organ can be produced using induced pluripotent stem (iPS) cells, says Takebe.

These iPS cells are made by converting mature cells such as skin cells into a state from which they can develop into many other cell types (see The Science of iPS Cells). The discovery that mature cells can be reprogrammed to this powerful state thats useful for experiments was the basis of the 2012 Nobel Prize in Physiology or Medicine.

The study provides a precedent for thinking about making organs and reconstructing more complex three-dimensional structures or tissues, says George Daley, director of the Stem Cell Transplantation program at Childrens Hospital in Boston. The researchers took a creative approach to building the proto-liver, says Daley, by co-mingling three different cell types: liver cell precursors derived from human iPS cells, blood vessel precursors called endothelial cells, and connective tissue precursor cells called mesenchymal stem cells. Both the blood vessel and connective tissue precursor cells were harvested from umbilical cords.

The findings from Takebe and his colleagues build upon existing work showing that co-culturing multiple cell types can help researchers develop physiological three-dimensional tissues in the lab, says Yoon-Young Jang, director of the Stem Cell Biology Laboratory at Johns Hopkins University School of Medicine. Other groups have also shown that stem cellswhen given the right chemical signalscan spontaneously develop into three-dimensional structures similar to natural tissues, such as the retina (see Growing Eyeballs).

The methods used by the researchers in the new study also mimic some aspects of the natural embryonic development of the liver. Adhering to the principles of developmental biology in this way is a strategy that many in the field of regenerative medicine are taking, says Daley. This study is a good example where generating a more ordered three-dimensional organoid is probably the route that most of us are going, he says. The ability of these organoids to mediate human liver-specific drug metabolism is a very impressive proof of principle for the utility of this approach.

To demonstrate the therapeutic potential of the liver bud method, Takebe and colleagues transplanted a dozen liver buds into the abdomen of mice whose natural liver function was shut down with a drug. The liver bud transplants kept these mice alive for the month they were watched.

The liver buds did not achieve all the functions of a mature liver. For instance, the buds did not form a bile duct system. However, in ongoing research, the team has found that by transplanting the buds into an existing liver, the body seems to make use of the existing bile system, Takebe said by email.

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A Proto-Liver Is Grown from Stem Cells

Health care

Maggie Fox, Senior Writer NBC News

July 3, 2013 at 1:02 PM ET

Yokohama City University/Nature

Japanese researchers have generated functioning human liver buds using a type of stem cell called an iPS cell. They grew these rudimentary livers in lab dishes and transplanted them into mice, where they acted like real human liver tissue.

Scientists have found a possible new way to grow a human liver from scratch, using stem cells that form a bud, then transplanting this growing baby liver into the body.

Their work may eventually offer a new way to try to help fill the growing need for organs for transplant. With nearly 17,000 people waiting for a liver transplant in the United States, according to the United Network for Organ Sharing, the need is dire.

Theyve only tried their approach in mice so far, and it would be years before they could start testing it in people. But they used human cells in their experiment and the little pieces of liver that grew in the mice functioned as human liver, not mouse liver.

It might be eventually possible to grow little liver buds and seed them throughout a damaged liver to help regenerate healthy tissue, the researchers report in the journal Nature.

Takanori Takebe, Hideki Taniguchi and colleagues at Yokohama City University in Japan used a certain type of stem cell called an induced pluripotent stem cell, or iPS cell. These cells can be generated using mature tissue like a piece of skin from someone. Theyre genetically manipulated to make them revert to an embryonic state, when each cell has the potential to become any type of tissue or organ in the body.

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Scientists grow working ‘baby’ liver from stem cells

A mixture of three cell types self-assembles into a liver bud that can be seen with the naked eye.

In work that will raise hope that organs could be repaired or even grown from scratch using a patients own tissue as the raw material, Japanese researchers have created functioning liver tissue from stem cells and successfully transplanted them into mice.

The researchers found that a mixture of human liver precursor cells and two other cell types can spontaneously form three-dimensional structures dubbed liver buds. In the mice, these liver buds formed functional connections with natural blood vessels and perform some liver-specific functions such as breaking down drugs in the bloodstream.

Its possible the technique will work with other organ types, including the pancreas, kidney, or lungs, lead author Takanori Takebe, a scientist at Yokohama City University in Japan, said Tuesday at a press conference, aided by a translator. The study, published in Nature on Wednesday, is the first demonstration that a rudimentary human organ can be produced using induced pluripotent stem (iPS) cells, says Takebe.

These iPS cells are made by converting mature cells such as skin cells into a state from which they can develop into many other cell types (see The Science of iPS Cells). The discovery that mature cells can be reprogrammed to this powerful state thats useful for experiments was the basis of the 2012 Nobel Prize in Physiology or Medicine.

The study provides a precedent for thinking about making organs and reconstructing more complex three-dimensional structures or tissues, says George Daley, director of the Stem Cell Transplantation program at Childrens Hospital in Boston. The researchers took a creative approach to building the proto-liver, says Daley, by co-mingling three different cell types: liver cell precursors derived from human iPS cells, blood vessel precursors called endothelial cells, and connective tissue precursor cells called mesenchymal stem cells. Both the blood vessel and connective tissue precursor cells were harvested from umbilical cords.

The findings from Takebe and his colleagues build upon existing work showing that co-culturing multiple cell types can help researchers develop physiological three-dimensional tissues in the lab, says Yoon-Young Jang, director of the Stem Cell Biology Laboratory at Johns Hopkins University School of Medicine. Other groups have also shown that stem cellswhen given the right chemical signalscan spontaneously develop into three-dimensional structures similar to natural tissues, such as the retina (see Growing Eyeballs).

The methods used by the researchers in the new study also mimic some aspects of the natural embryonic development of the liver. Adhering to the principles of developmental biology in this way is a strategy that many in the field of regenerative medicine are taking, says Daley. This study is a good example where generating a more ordered three-dimensional organoid is probably the route that most of us are going, he says. The ability of these organoids to mediate human liver-specific drug metabolism is a very impressive proof of principle for the utility of this approach.

To demonstrate the therapeutic potential of the liver bud method, Takebe and colleagues transplanted a dozen liver buds into the abdomen of mice whose natural liver function was shut down with a drug. The liver bud transplants kept these mice alive for the month they were watched.

The liver buds did not achieve all the functions of a mature liver. For instance, the buds did not form a bile duct system. However, in ongoing research, the team has found that by transplanting the buds into an existing liver, the body seems to make use of the existing bile system, Takebe said by email.

Continued here:
A Rudimentary Liver Is Grown from Stem Cells

Scientists have created a tiny liver from stem cells that helped mice with chronic liver failure regain function.

Researchers in Japan transplanted 4-millimeter-wide "liver buds" made from human stem cells into a mice. The transplanted liver buds, which were placed in the cranium or abdomen, were able to work in conjunction with the mice's own organs and secrete human liver-specific proteins. They also created human metabolites, tiny molecules that are produced when the body metabolizes a substance.

Co-author Takanori Takebe, a stem-cell biologist at Yokohama City University in Japan, said to Nature this was the first time people have made a solid organ using pluripotent stem cells, which are mature skin cells that are re-programmed to become an embryonic cell that can express any genetic characteristics.

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In this case, the liver buds were made from pluripotent stem cells that were told to express liver genes. Endothelial cells (which line blood vessels) taken from umbilical chord blood and mesenchymal stem cells (which make bone, cartilage and fat) were put into the mix as well.

"We just simply mixed three cell types and found that they unexpectedly self-organize to form a three-dimensional liver bud -- this is a rudimentary liver," Takebe explained to the BBC. "And finally we proved that liver bud transplantation could offer therapeutic potential against liver failure."

After hundreds of trials, the three cells worked together and began to make three-dimensional structures. Takebe admitted he was "absolutely surprised" when he saw it working.

According to the Organ Procurement and Transplantation Network, there are currently more than 16,500 people registered on the liver transplant waiting list. There were only 6,256 people who received a liver transplant in 2012.

Takebe said that human transplantation is still years away, and the research is very preliminary. The mice still need be observed to see if the liver buds continue to function or tumors start to form. Also, the liver buds will never be able to grow into a full liver, but they could one day work with a failing liver and help restore its function. He hopes in the future researchers can create liver buds small enough to be transfused intravenously, and forsees that this method could also be used to create new pancreas or kidney cells.

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Researchers create miniature human liver out of stem cells