Category Archives: Stem Cells

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.

Read more:
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.

See original here:
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.

See the rest here:
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.

Play Video

Play Video

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.

Read the original:
Researchers create miniature human liver out of stem cells

SINGAPORE, July 2 (Bernama) -- Scientists in Singapore and Germany have discovered a molecular network in human embryonic stem cells (hESCs) that integrates cell communication signals to keep the cell in its stem cell state.

In a statement, A*STAR's Genome Institute of Singapore (GIS) said these findings by the institute and the Max Planck Institute for Molecular Genetics (MPIMG) in Berlin, were reported in the June 2013 issue of Molecular Cell.

Many factors are required for stem cells to keep their special state, among others is the use of cell communication pathways.

Cell communication is of key importance in multicellular organisms, such as the coordinated development of tissues in the embryo so that cells receive signals and respond accordingly.

If there are errors in the signals, the cell will respond differently, possibly leading to diseases such as cancer.

The communication signals which are used in hESCs activate a chain of reactions (called the extracellular regulated kinase (ERK) pathway) within each cell, causing the cell to respond by activating genetic information.

The authors propose a model that integrates this bi-directional control to keep the cell in the stem cell state.

These findings are particularly relevant for stem cell research, but they might also help research in other related fields.

First author Dr Jonathan Goke from Stem Cell and Developmental Biology at the GIS said: "The ERK signalling pathway has been known for many years, but this is the first time we are able to see the full spectrum of the response in the genome of stem cells.

"We have found many biological processes that are associated with this signaling pathway, but we also found new and unexpected patterns such as this dual mode of ELK1.

Read more here:
Scientists In Singapore, Germany Discover Network In Human Stem Cells

Singapore, July 2, 2013 - (ACN Newswire) - Scientists at A*STAR's Genome Institute of Singapore (GIS) and the Max Planck Institute for Molecular Genetics (MPIMG) in Berlin (Germany) have discovered a molecular network in human embryonic stem cells (hESCs) that integrates cell communication signals to keep the cell in its stem cell state. These findings were reported in the June 2013 issue of Molecular Cell.

Human embryonic stem cells have the remarkable property that they can form all human cell types. Scientists around the world study these cells to be able to use them for medical applications in the future. Many factors are required for stem cells to keep their special state, amongst others the use of cell communication pathways.

Cell communication is of key importance in multicellular organisms. For example, the coordinated development of tissues in the embryo to become any specific organ requires that cells receive signals and respond accordingly. If there are errors in the signals, the cell will respond differently, possibly leading to diseases such as cancer. The communication signals which are used in hESCs activate a chain of reactions (called the extracellular regulated kinase (ERK) pathway) within each cell, causing the cell to respond by activating genetic information.

Scientists at the GIS and MPIMG studied which genetic information is activated in the cell, and thereby discovered a network for molecular communication in hESCs. They mapped the kinase interactions across the entire genome, and discovered that ERK2, a protein that belongs to the ERK signaling family, targets important sites such as non-coding genes and histones, cell cycle, metabolism and also stem cell-specific genes.

The ERK signaling pathway involves an additional protein, ELK1 which interacts with ERK2 to activate the genetic information. Interestingly, the team also discovered that ELK1 has a second, totally opposite function. At genomic sites which are not targeted by ERK signaling, ELK1 silences genetic information, thereby keeping the cell in its undifferentiated state. The authors propose a model that integrates this bi-directional control to keep the cell in the stem cell state.

These findings are particularly relevant for stem cell research, but they might also help research in other related fields.

First author Dr Jonathan Goke from Stem Cell and Developmental Biology at the GIS said, "The ERK signaling pathway has been known for many years, but this is the first time we are able to see the full spectrum of the response in the genome of stem cells. We have found many biological processes that are associated with this signaling pathway, but we also found new and unexpected patterns such as this dual mode of ELK1. It will be interesting to see how this communication network changes in other cells, tissues, or in disease."

"A remarkable feature of this study is, how the information was extracted by computational means from the experimental data," said Prof Martin Vingron from MPIMG and co-author of this study.

Prof Ng Huck Hui added, "This is an important study because it describes the cell's signaling networks and its integration into the general regulatory network. Understanding the biology of embryonic stem cells is a first step to understanding the capabilities and caveats of stem cells in future medical applications."

Notes to the Editor:

See the article here:
Genome Institute of Singapore Scientists Discover Molecular Communication Network in Human Stem Cells

July 1, 2013 Vitamin C affects whether genes are switched on or off inside mouse stem cells, and may thereby play a previously unknown and fundamental role in helping to guide normal development in mice, humans and other animals, a scientific team led by UC San Francisco researchers has discovered.

The researchers found that vitamin C assists enzymes that play a crucial role in releasing the brakes that keep certain genes from becoming activated in the embryo soon after fertilization, when egg and sperm fuse.

The discovery might eventually lead to the use of vitamin C to improve results of in vitro fertilization, in which early embryos now are typically grown without the vitamin, and also to treat cancer, in which tumor cells abnormally engage or release these brakes on gene activation, the researchers concluded in a study published June 30, 2013 in the journal Nature.

In the near term, stem-cell scientists may begin incorporating vitamin C more systematically into their procedures for growing the most healthy and useful stem cells, according to UCSF stem-cell scientist Miguel Ramalho-Santos, PhD, who led the study. In fact, the unanticipated discovery emerged from an effort to compare different formulations of the growth medium, a kind of nutrient broth used to grow mouse embryonic stem cells in the lab.

Rather than building on any previous body of scientific work, the identification of the link between vitamin C and the activation of genes that should be turned on in early development was serendipitous, Ramalho-Santos said. "We bumped into this result," he said.

Working in Ramalho-Santos' lab, graduate student Kathryn Blaschke and postdoctoral fellow Kevin Ebata, PhD, were comparing different commercial growth media for mouse stem cells. The researchers began exploring how certain ingredients altered gene activity within the stem cells. Eventually they discovered that adding vitamin C led to increased activity of key enzymes that release the brakes that can prevent activation of an array of genes.

The brakes on gene activation that vitamin C helps release are molecules called methyl groups. These methyl groups are added to DNA at specific points along the genome to prevent specific genes from getting turned on.

During the development of multicellular organisms, humans among them, different patterns of methylation arise in different cells as methyl groups are biochemically attached to DNA at specific points along the genome during successive cell divisions. Normally this gradual methylation, a key part of the developmental program, is not reversible.

But after fertilization and during early development, a class of enzymes called "Tet" acts on a wide array of the methyl groups on the DNA to remove these brakes, so that genes can be activated as needed.

The UCSF researchers demonstrated that Tet enzymes require vitamin C for optimal activity as they act to remove the methyl groups from the DNA and to stimulate gene activity that more faithfully mimics in cultured stem cells what occurs at early stages of development in the mouse embryo.

Read the original here:
Vitamin C helps control gene activity in stem cells

July 2, 2013 Scientists at A*STAR's Genome Institute of Singapore (GIS) and the Max Planck Institute for Molecular Genetics (MPIMG) in Berlin (Germany) have discovered a molecular network in human embryonic stem cells (hESCs) that integrates cell communication signals to keep the cell in its stem cell state. These findings were reported in the June 2013 issue of Molecular Cell.

Human embryonic stem cells have the remarkable property that they can form all human cell types. Scientists around the world study these cells to be able to use them for medical applications in the future. Many factors are required for stem cells to keep their special state, amongst others the use of cell communication pathways.

Cell communication is of key importance in multicellular organisms. For example, the coordinated development of tissues in the embryo to become any specific organ requires that cells receive signals and respond accordingly. If there are errors in the signals, the cell will respond differently, possibly leading to diseases such as cancer. The communication signals which are used in hESCs activate a chain of reactions (called the extracellular regulated kinase (ERK) pathway) within each cell, causing the cell to respond by activating genetic information.

Scientists at the GIS and MPIMG studied which genetic information is activated in the cell, and thereby discovered a network for molecular communication in hESCs. They mapped the kinase interactions across the entire genome, and discovered that ERK2, a protein that belongs to the ERK signaling family, targets important sites such as non-coding genes and histones, cell cycle, metabolism and also stem cell-specific genes.

The ERK signaling pathway involves an additional protein, ELK1 which interacts with ERK2 to activate the genetic information. Interestingly, the team also discovered that ELK1 has a second, totally opposite function. At genomic sites which are not targeted by ERK signaling, ELK1 silences genetic information, thereby keeping the cell in its undifferentiated state. The authors propose a model that integrates this bi-directional control to keep the cell in the stem cell state.

These findings are particularly relevant for stem cell research, but they might also help research in other related fields.

First author Dr Jonathan Gke from Stem Cell and Developmental Biology at the GIS said, "The ERK signaling pathway has been known for many years, but this is the first time we are able to see the full spectrum of the response in the genome of stem cells. We have found many biological processes that are associated with this signaling pathway, but we also found new and unexpected patterns such as this dual mode of ELK1. It will be interesting to see how this communication network changes in other cells, tissues, or in disease."

"A remarkable feature of this study is, how the information was extracted by computational means from the experimental data," said Prof Martin Vingron from MPIMG and co-author of this study.

Prof Ng Huck Hui added, "This is an important study because it describes the cell's signaling networks and its integration into the general regulatory network. Understanding the biology of embryonic stem cells is a first step to understanding the capabilities and caveats of stem cells in future medical applications."

See the rest here:
Scientists discover molecular communication network in human stem cells