Category Archives: Stem Cells

October 5, 2012

Lee Rannals for redOrbit.com Your Universe Online

Japanese scientists reported in the journal Science that they have created life using stem cells made from skin.

The skin cells were used to create eggs which were then fertilized to produce baby mice, who later had their own babies.

The technique has implications that may possibly help infertile couples have children, and maybe could even allow women to overcome menopause.

About one in 10 women of childbearing age face trouble becoming a parent, according to the Centers for Disease Control and Prevention (CDC).

Last year, the scientists at Kyoto University were able to make viable sperm from stem cells. In the more recent study, the team was able to perform a similar accomplishment with eggs.

The researchers used two sources, including those collected from an embryo and skin-like cells, that were reprogrammed into becoming stem cells.

After turning the stem cells into early versions of eggs, they rebuilt an ovary by surrounding the early eggs with other types of supporting cells normally found in an ovary.

They used IVF techniques to collect the eggs, fertilize them with sperm from a male mouse and implant the fertilized egg into a surrogate mother.

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Healthy Mice Created From Skin Stem Cells In Lab

Queensland scientists will investigate the genetic pathway of ovarian cancer stem cells in a bid to better understand the aggressive disease.

Dr Ying Dong and Professor Judith Clements from Queensland University of Technology have shown previously that secondary ovarian cancer tumour cells are resistant to chemotherapy.

'The key to fighting this cancer could be to identify the molecular or gene pathways that regulate it, such as the stem cells,' said Dr Dong.

'They are the cells that change and build resistance to the chemotherapy.'

The team's collaborators in India, including Dr Sharmila Bapat, were the first in the world to identify ovarian cancer stem cells.

Dr Bapat's team will use 3D modelling by Dr Dong to mimic the environment of tumours and study how ovarian cancer cells respond to chemotherapy.

'Together, we will investigate the role of these pathways and test their potential as therapeutic targets,' Dr Dong said.

'We hope we will be able to help design more effective treatment for women with ovarian cancer with this knowledge.'

Link:
Ovarian cancer stem cells investigated

By Dennis Normile, ScienceNOW

Want baby mice? Grab a petri dish. After producing normal mouse pups last year using sperm derived from stem cells, a Kyoto University team of researchers has now accomplished the same feat using eggs created the same way. The study may eventually lead to new ways of helping infertile couples conceive.

This is a significant achievement that I believe will have a sustained and long-lasting impact on the field of reproductive cell biology and genetics, says Amander Clark, a stem cell biologist at University of California, Los Angeles.

The stem cells in both cases are embryonic stem (ES) cells and induced pluripotent stem (iPS) cells. The former are taken from embryos and the latter are adult tissue cells that are reprogrammed to act like stem cells. In theory, both can produce all of the bodys cell types, yet most researchers have been unable to turn them into germ cells, precursors of sperm and eggs.

The Kyoto group, led by stem cell biologist Mitinori Saitou, found a process that works. As with the sperm, the group started with ES and iPS cells and cultured them in a cocktail of proteins to produce primordial germ cell-like cells. To get oocytes, or precursor egg cells, they then mixed the primordial cells with fetal ovarian cells, forming reconstituted ovaries that they then grafted onto natural ovaries in living mice. Four weeks and 4 days later, the primordial germ cell-like cells had developed into oocytes. The team removed the ovaries, harvested the oocytes, fertilized them in vitro, and implanted the resulting embryos into surrogate mothers. About 3 weeks later, normal mouse pups were born, the researchers report online today in Science.

It is remarkable that one can produce oocytes capable of sustaining complete development starting with embryonic stem cells, says Davor Solter, a developmental biologist at Singapores Institute of Medical Biology. Clark adds that the immediate impact of the work will be on understanding the molecular mechanisms involved in forming germ cells. Saitou says that with a bit more progress in understanding the complex interactions at work, they may be able to coax the cells through the entire oocyte development process in a lab dish. If successful, we may be able to skip the grafting, he says.

Further in the future, the technique could lead to a new tool for treating infertility. This study has provided the critical proof of principle that oocytes can be generated from induced pluripotent stem cells, Clark says. If applied to humans, it could lead to the ability to create oocytes from iPS cells taken from infertile women. But Saitou cautions that moving on to human research will require resolving thorny ethical issues and technical difficulties. Solter says that at the extreme, the new approach could lead to the production of human embryos from cell lines and tissue samples. Still, he notes, defining the status of such parentless human embryos and the biological, ethical, and legal issues they will raise defies the imagination.

This story provided by ScienceNOW, the daily online news service of the journal Science.

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Dish-Grown Sperm and Eggs Produce Mouse Pups

And rightly so: stem-cell scientists have derived many types of cells from stem-cell precursors, but have in the past struggled with sex cells. The research by a team at Kyoto University provides a powerful model into mammalian development and infertility, but it is still a long way off from being used in human therapy.

Despite this fact, it did not stop the headlines in some of today's press screaming that infertile women could one day become pregnant by creating eggs from stem cells.

Evelyn Telfer, a reproductive biologist at the University of Edinburgh, told me this study has no clinical application to humans whatsoever because the tissue used in this study were all foetal and not adult cells.

Mitinori Saitou led a team using foetal mouse tissue from embryos or skin cells to create stem cells. Those stem cells were then genetically reprogrammed to become germ cells egg precursor cells.

These were then given a cocktail of "factors" to support their growth into mature eggs. The eggs were fertilised by IVF in the lab and then implanted into surrogate mice. Three baby mice were born and grew into fertile adults.

The fact that artificially manufactured eggs have gone on to produce healthy mice which are fertile is absolutely astounding and a great step forward for science. The results are published in the journal, Science.

But there are huge differences between human and mouse cells, not to mention the medical and ethical issues surrounding human ovarian tissue to culture cells.

Further clinical trials would be necessary using adult mouse cells first before we can start projecting that we can manufacture babies, and scientists need to learn so much more about how women form eggs.

So while this is major contribution to the field of reproductive biology, the study is not a ready-made cure for women with fertility problems.

Originally posted here:
Stem cells: of mice and women?

Mouse eggs can now be cooked up from scratch. Using stem cells, a Japanese team has created healthy eggs that, once fertilised, grow into normal mouse pups.

Both egg and sperm cells start life as primordial germ cells (PGCs). Last year, Katsuhiko Hayashi and his colleagues at Kyoto University in Japan found they could generate PGC-like cells from either mouse embryonic stem cells or body cells that can turn into stem cells known as induced pluripotent stem cells or IPSCs. What's more, the team managed to coax these PGC-like cells into becoming sperm (Cell, DOI: 10.1016/j.cell.2011.06.052).

Now Hayashi and his colleagues have created eggs from the PGC-like cells. They started with embryonic stem cells and IPSCs taken from a female mouse embryo. In separate experiments, the team coaxed each type of stem cell to form PGC-like cells. When these cells were surrounded by ovary cells, also taken from a mouse embryo, they formed immature egg cells.

The team implanted these young egg cells into the ovaries of adult mice. Four weeks later, when Hayashi's team removed the ovaries, they found the cells had developed into mature eggs. When these eggs were fertilised with sperm and implanted into other mice, they were able to form embryos that developed into healthy mouse pups.

"It's an amazing result," says Evelyn Telfer at the University of Edinburgh, UK, who was not involved in the work.

The success of the PGC-like cells suggests that these induced cells are very similar to the PGCs found in the body, says Hayashi. It's difficult to study PGCs themselves because they are so rare, says Hayashi.

"We will be able to identify factors involved in PGC development," he says. "We expect that some of these are [the same] in humans [as in mice], and that they are responsible for human disease."

Unfortunately, not all of the embryos developed normally. The team couldn't tell whether the abnormalities were a result of problems with the egg cells themselves or their growth environment. "[They'll] need to optimise the system," says Telfer.

Once the wrinkles have been ironed out, it would be possible, in theory, to fertilise stem-cell-derived eggs with stem-cell-derived sperm, Telfer says. "If you took the stem cells from the same individual you could avoid sexual reproduction," she says, half-jokingly.

In the meantime, stem-cell-derived egg and sperm cells hold the most promise for people with fertility problems. If the team can derive egg and sperm cells from adult stem cells, individuals who have become infertile because of harsh cancer therapies for example could potentially generate new sperm or eggs from their own body cells.

Read more:
Mouse eggs created from stem cells for the first time

Stem cells have been coaxed into creating everything from liver cells to beating heart tissue. Recently, these versatile cells were even used to make fertile mouse sperm, suggesting that stem cell technology might eventually be able to play a role in the treatment of human infertility. Now two types of stem cells have been turned into viable mouse egg cells that were fertilized and eventually yielded healthy baby mice. Details of this achievement were published online October 4 in Science. Katsuhiko Hayashi, of Kyoto University's School of Medicine, were able to create the eggs with embryonic stem cells as well as with induced pluripotent stem cells (formed from adult cells). The team started with female embryonic stem cells and then coaxed them genetically to revert to an earlier developmental stage (primordial germ cell-like cells). These cells were blended with gonadal somatic cells, important in the development of sexual differentiation, to create "reconstituted ovaries." The researchers then transplanted these cultured assemblages into female mice (in either the actual ovary or the kidney) for safekeeping and to allow the stem cells to mature into oocytes in a natural environment. To test the eggs' fertility, the new oocytes were removed from the mice for an in vitro fertilization with mouse spermand then re-implanted into the female mice. The experimental females went on to bear normally developing and fertile offspring. The procedure was then also performed successfully with induced pluripotent stem cells from adult skin cells with similar results. "Our system serves as a robust foundation to investigate and further reconstitute female germline development in vitro," the researchers noted in their paper," not only in mice, but also in other mammals, including humans."

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Baby Mice Born from Eggs Made from Stem Cells

In a long-sought achievement, Japanese researchers have demonstrated in mice that both eggs and sperm can be grown from stem cells and combined to produce healthy offspring, pointing the way to a new avenue for fertility treatments.

If the milestone accomplishment can be repeated in humans -- and experts said they are optimistic that such efforts will ultimately succeed -- the technique could make it easier for women in their 30s or 40s to become mothers. It could also help men and women whose reproductive organs have been damaged by cancer treatments or other causes.

About 10% of American women of childbearing age have trouble becoming or staying pregnant, and more than one-third of infertile couples must contend with a medical problem related to the prospective father, according to the U.S. Centers for Disease Control and Prevention in Atlanta.

Using current technology, only about one-third of attempts at assisted reproduction result in live births, CDC data show. Scientists, doctors and patients would like to boost that percentage.

"These studies provide that next level of evidence that in the future fertility could be managed with stem cell intervention," said Teresa Woodruff, chief of fertility preservation at Northwestern University's Feinberg School of Medicine.

The prospect of using stem cells to grow new eggs is particularly tantalizing, because women are born with a set amount and don't make more once they are lost. In a sense, the therapy would allow them to turn back their biological clocks, said Stanford stem cell researcher Renee A. Reijo Pera, who studies reproduction.

"This is a get-them-back strategy," she said.

Using stem cells to create sperm and eggs in mice is a feat researchers have attempted, without much success, for more than a decade, said Dr. George Q. Daley, a leading stem cell researcher at Children's Hospital in Boston.

Dr. Mitinori Saitou and colleagues at Kyoto University detailed how they generated the functional mouse eggs in a report published online Thursday by the journal Science. Last year, the researchers reported in the journal Cell that they had done the same thing with mouse sperm.

In both cases, the team started with embryonic stem cells, which have the potential to develop into all of the different types of cells in the body. The scientists exposed the embryonic stem cells to stimuli that coaxed them to become egg and sperm precursors.

Originally posted here:
Stem cells could lead to future fertility treatments, study says

Mouse pups created using lab-made eggs went on to be fully fertile themselves.

Courtesy of Katsuhiko Hayashi

Japanese researchers have coaxed mouse stem cells into becoming viable eggs that produce healthy offspring1. The work provides a powerful tool to study basic elements of mammalian development and infertility that have long been shrouded in mystery.

People have been trying to make sex cells from embryonic stem cells and from pluripotent cells for years, says Evelyn Telfer, a reproductive biologist at the University of Edinburgh, UK. Theyve done it and theyve done it really well.

Stem-cell scientists have derived many types of cells from stem-cell precursors, but have struggled with sex cells. These cells have significantly more complex developmental programmes, in part because of the difference in the way they divide. Most cells in the body undergo mitosis, in which both sets of chromosomes are copied, but sex cells are produced by meiosis, which results in cells containing a single copy of each chromosome.

Last year, the same team from Mitinori Saitous lab at Kyoto University in Japan successfully used mouse stem cells to make functional sperm2. Whereas sperm cells are some of the simpler cells in the body, oocytes are much more complex.

It was always believed that making sperm was probably easier, says Davor Solter, a developmental biologist at the Institute of Medical Biology in Singapore, who was not involved with the study. The oocyte is the thing which makes the whole of development possible.

In the latest study, published today in Science, Saitou and his colleagues started with two cell types: mouse embryonic stem cells and induced pluripotent stem cells, which can be derived from adult cells. Just as in the earlier sperm study, they used a cocktail of signalling molecules to transform the stem cells first into epiblast cells and then into primordial germ cells (PGCs), both egg precursors. Whereas male PGCs could be injected directly into infertile male mice to mature into sperm, the female version required further coddling.

The researchers isolated embryonic ovary tissue that did not contain sex cells and then added their lab-made PGCs to the dish. The mixture spontaneously formed ovary-like structures, which they transplanted into female mice. After four weeks, the stem-cell-derived PGCs had matured into oocytes. The team fertilized them and transplanted the embryos into foster mothers. The offspring that were produced grew up to be fertile themselves.

PGCs are scarce and difficult to isolate from mice, so researchers know little about their regulation, says Saitou. As PGCs develop into sperm or egg cells, certain genes are silenced in a process called genomic imprinting. Although this is crucial for development, little is known about how it starts or how genes are selected for silencing.

The rest is here:
Mouse stem cells lay eggs

Experimental approach might provide insights to support human fertility

Web edition : 2:01 pm

Some baby mice born in Japan are living proof that mouse stem cells taken from embryos or created by reprogramming fetal tissue can be used to make viable egg cells.

Researchers had already created functional sperm from stem cells, and some groups have reported making eggs, or oocytes, but those had never been shown to produce offspring. Now, Mitinori Saitou of Kyoto University in Japan and colleagues have coaxed mouse stem cell to make eggs that produce normal, fertile offspring, the researchers report online October 4 in Science.

This is really pioneering research, says Charles Easley, a reproductive stem cell biologist at Emory University School of Medicine in Atlanta.

The researchers have gone a step beyond making cells that merely look like eggs in a lab dish. This paper produces something that looks like oocytes, smells like oocytes and tastes like oocytes in a way no one has done before, says David Albertini, a reproductive scientist at the University of Kansas Medical Center in Kansas City.

While the evidence that the Japanese researchers have transformed mouse stem cells into functional female gametes is compelling, Albertini doesnt think the feat will be repeated with human stem cells because they are far less flexible than their mouse counterparts. The new technology might provide a way to test the effect that chemicals in the environment may have on fertility and give scientists new information about how eggs age, possibly leading to fertility-extending treatments, he says.

In the new study, Saitou and colleagues started with stem cells from very early mouse embryos as well as stem cells reprogrammed from fetal cells, known as induced pluripotent stem cells. Saitous team manipulated the activity of a few genes in the stem cells to turn them into cells that resemble precursors of gametes, as eggs and sperm are sometimes known.

These primordial germ celllike cells, as they are called, were mixed with support cells from an embryonic ovary and then transplanted into adult mice. Once the precursor cells had developed into oocytes, the researchers pulled them out and fertilized them in the lab before implanting the resulting embryos in female mice.

The oocytes made from either type of stem cell produced mouse pups 3.9 percent of the time. That rate is lower than for primordial germ cells taken directly from mouse embryos, which the researchers found produced pups 17.3 percent of the time. Oocytes taken from the ovaries of 3-week-old mice generated offspring 12.7 percent of the time. Female pups resulting from stem cellderived eggs grew up to become fertile adults, the researchers report.

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Mouse stem cells yield viable eggs