Category Archives: Stem Cell Videos

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.

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Stem cells: of mice and women?

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

A team of Japanese scientists has managed to turn mouse stem cells into viable eggsthat can be inseminated and go on to produce normal, healthy mouse pups. The finding has massive implications for the development of infertility treatments in the future.

The team of researchers from Kyoto University has previously created fully grown adult mice using sperm created from stem cellsbut that's comparatively straightforward. Sperm, you see, are some of the simpler cells in the body: eggs are far more complex.

In this new study, published in Science, the researchers took embryonic stem cells, and induced pluripotent stem cells (iPSCs) from them. They then used a host of signaling molecules to slowly transform the iPSCs into egg precursors known as primordial germ cells. After further coddling in lab-grown ovary tissue, the cellsover the course of four weeksmatured into eggs.

The scientists fertilized these eggs and transplanted the resulting embryos in to foster mothers. A short while later, healthy offspring emerged, which went on to become fertile themselves. All in, it's a long and involved processbut, amazingly, it works.

The finding gives a useful glimpse into the processes at play during meiosis, the cell-division process which is peculiar to sex cells like eggs. But perhaps more interesting are the possibilities for the development of new infertility treatments in the future.

As ever, just because something's possible in a mouse doesn't mean it will necessarily work in a human model, but that won't stop the team trying: indeed, they're already starting to work with human stem cells instead. Expect a wait before you hear of this kind of technology being used in a clinical, as opposed to research, setting, though, because the ethical issues surrounding it will be close to impossible to settle. [Science via Nature]

Image by angeladellatorre under Creative Commons license

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Scientists Create Healthy Mice Using Eggs Made From Stem Cells [Science]

London, October 5 (ANI): Using stem cells made from skin, a Japanese team has created healthy eggs that, once fertilised, grow into normal baby mice.

These babies later had their own babies, the BBC reported.

The team at Kyoto University used stem cells from two sources: those collected from an embryo and skin-like cells, which were reprogrammed, into becoming stem cells.

The first step was to turn the stem cells into early versions of eggs.

A "reconstituted ovary" was then built by surrounding the early eggs with other types of supporting cells that are normally found in an ovary. This was transplanted into female mice. Surrounding the eggs in this environment helped them to mature.

IVF techniques were used to collect the eggs, fertilise them with sperm from a male mouse and implant the fertilised egg into a surrogate mother.

"They develop to be healthy and fertile offspring," Dr Katsuhiko Hayashi, from Kyoto University, told the BBC.

Those babies then had babies of their own, whose "grandmother" was a cell in a laboratory dish.

If the same methods could be used in people then, it could help infertile couples have children and even allow women to overcome the menopause.

But experts say many scientific and ethical hurdles must be overcome before the technique could be adapted for people.

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Life created for first time from eggs made from skin cells

Experimental approach might provide insights to support human fertility

Web edition : Thursday, October 4th, 2012

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

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.

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Mouse stem cells lay eggs

4 October 2012 Last updated at 18:31 ET By James Gallagher Health and science reporter, BBC News

Stem cells made from skin have become "grandparents" after generations of life were created in experiments by scientists in Japan.

The cells were used to create eggs, which were fertilised to produce baby mice. These later had their own babies.

If the technique could be adapted for people, it could help infertile couples have children and even allow women to overcome the menopause.

But experts say many scientific and ethical hurdles must be overcome.

Stem cells are able to become any other type of cell in the body from blood to bone, nerves to skin.

Last year the team at Kyoto University managed to make viable sperm from stem cells. Now they have performed a similar feat with eggs.

They used stem cells from two sources: those collected from an embryo and skin-like cells which were reprogrammed into becoming stem cells.

I just thought wow! The science is quite brilliant

The first step, reported in the journal Science, was to turn the stem cells into early versions of eggs.

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Skin cells become 'grandparents'

Public release date: 3-Oct-2012 [ | E-mail | Share ]

Contact: Marla Paul Marla-Paul@northwestern.edu 312-503-8928 Northwestern University

Researchers at Northwestern University Feinberg School of Medicine have developed the first animal model that duplicates the human response in rheumatoid arthritis (RA), an important step that may enable scientists to discover better medicines to treat the disease.

Corresponding and senior author Harris Perlman, associate professor of rheumatology at Feinberg, introduced his team's new prototype mouse model in a recent online issue of the Journal of Translational Medicine.

"This is the first time human stem cells have been transplanted into mice in order to find RA treatments," Perlman said. "We believe this will improve drug discovery because the reactions we observed were authentic human reactions."

Until now, scientists have relied on the common scientific method of using specially bred mice to find drugs to control RA. However, human and mouse immune systems differ dramatically, so studying RA in these mice does not give an accurate representation of how the disease functions in humans. In some cases, RA drugs that seemed promising based on results in mice failed in human clinical trials.

Mice implanted with human stem cells have been used before mainly to study infectious disease.

The Northwestern team injected day-old mice with human stem cells from umbilical cord blood, including white blood cells, which regulate immunity. Then, RA was introduced in the mice and suppressed with Enbrel, a common first-line drug for joint inflammation in humans. This offered evidence that their immune systems were indeed replicating human defenses.

Scientists seek mouse models that mimic RA in humans in order to learn how the complex disease operates. In the last decade, researchers and physicians have found many subtypes of RA that originate on the molecular level and are each produced by different pathways in the body.

A debilitating disease, rheumatoid arthritis is a chronic autoimmune disorder characterized by persistent inflammation around joint areas, predominantly in the wrist and fingers. The disease causes pain, swelling, stiffness and loss of function and can result in tissue destruction. Approximately 1.3 million people have the disease.

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'Humanized' mice advance study of rheumatoid arthritis

Pluristem Therapeutics Ltd. (Nasdaq:PSTI; DAX: PJT: PLTR) today announced that it has developed a portable instrument for thawing its placenta-based stems cell (PLX cells) on-site before they are administered to patients.

Pluristem will ship its off-the-shelf PLX cell therapy product candidates, which will be stored in multiple dose vials that require thawing prior to use. The vial will be placed into the proprietary thawing device and PLX cells will be ready for a convenient intramuscular injection. The company said that if the trials of the instrument are successful, it will be used as the final step in bringing high quality, clinical grade PLX cell products to patients around the globe.

"Pluristem understands the importance of providing a standardized product with every dose of these living drug delivery devices," said Pluristem chairman and CEO Zami Aberman. "If we are successful, we want our PLX cell products, once developed, to be an easy-to-use therapy. This thawing device will give us better control of several variables in our clinical trials and in treating patients after our products have been approved assuming we are successful. This instrument is an additional step in our vision to bring PLX cells as first-line therapies for a variety of indications and to think about the cell delivery process all the way from mass manufacturing to the patient's bedside."

Pluristem's share price rose 4.3% on the TASE today to NIS 16.05, after the announcement, after rising 4.4% on Nasdaq yesterday to $4.07, giving a market cap of $193 million.

Published by Globes [online], Israel business news - http://www.globes-online.com - on October 4, 2012

Copyright of Globes Publisher Itonut (1983) Ltd. 2012

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Pluristem unveils portable stem cells thawing device