Category Archives: Stem Cells

A new study has shown that reprogramming stem cells could help prevent cancer post radiation.

A University of Colorado Cancer Center study showed that one of the ways to get rid of such stem cells is a "program" that makes stem cells damaged by radiation differentiate into other cells that can no longer survive forever.

The study also showed that this same safeguard of "programmed mediocrity" that weeds out stem cells damaged by radiation allows blood cancers to grow in cases when the full body is irradiated. And by reprogramming this safeguard, it was possible to prevent cancer in the aftermath of full body radiation.

James DeGregori, PhD, the paper's senior author, who along with his colleagues explored the effects of full body radiation on the blood stem cells of mice, said that the body didn't evolve to deal with leaking nuclear reactors and CT scans. It evolved to deal with only a few cells at a time receiving dangerous doses of radiation or other insults to their DNA.

DeGregori found that mutations and other genetic alterations resulting in inhibition of the C/EBPA gene were associated with acute myeloid leukemia in humans. Thus, it wasn't mutations caused by radiation but a blood system reengineered by faulty stem cells that created cancer risk in people who had experienced radiation.

The studies show that by activating a stem cell maintenance pathway, it was possible to keep it from happening. Even months after irradiation, artificially activating the NOTCH signaling pathway of irradiated HSCs lets them act "stemmy" again - restarting the blood cell assembly line in these HSCs that would have otherwise differentiated in response to radiation.

When DeGregori, Fleenor and colleagues activated NOTCH in previously irradiated HSCs, it kept the population of dangerous, C/EBPA cells at bay. Competition from non-C/EBPA-mutant stem cells, with their fitness restored by NOTCH activation, meant that there was no evolutionary space for C/EBPA-mutant stem cells.

The study is published in the journal Stem Cells.

(Posted on 31-12-2014)

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Reprogrammed stem cells may stop cancer post radiation

Scientists are now creating primordial germ cells (precursors to egg and sperm) with human stem cells and even skin cells. This new work,published inCelltoday, takes us beyond what was previously just done using stem cells.

One of the first events in the early development of both mice and men is the creation of primordial germ cells (PGCs). After an egg is fertilized by sperm, embryonic stem cells begin to differentiate into various basic cell types that make up the fetus. A small number of these stem cellsdevelop into primordial germ cells, which will go on to become egg or sperm. Germ cells are immortal in the sense that they provide an enduring link between all generations, carrying genetic information from one generation to the next,Cambridges Azim Suranisays in auniversity statement.

Researchers have now figured out how to reprogram cells to act like embryonic stem cells. These induced pluripotent stem (iPS) cells have been used to develop humanretinasandintestines, for example, according to IFLScience. Researchers have also created iPS cells that could differentiate into primordial germ cells, but its only been successful in rodents.

Now, a team of researchers from the U.K. and Israel traced the genetic chain of events that directs a human stem cell to develop into a primordial germ cell. This stage in our development is called specification,and once PGCs become specified,they continue developing toward precursor sperm cells or ova pretty much on autopilot,Jacob Hanna from the Weizmann Institute of Sciencesays in anews release.

A master gene called SOX17 works to direct stem cells which in previous studies was found to direct stem cells into becoming lung, gut and pancreas cells. But the gene working as part of primordial germ cell specification is a new development.

The international team followed their discovery by actually making primordial germ cells in the lab. Using both embryonic stem cells and iPS cells (reprogrammed adult skin cells) from both males and females, the researchersmade sex cell precursors with up to 40 percent efficiency. When they compared the protein markers of their new, lab-grown PGCs with real PGCs collected from aborted fetuses,Nature reports, they were found to be very similar.

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Skin cells are being used to create artificial sperm and eggs

CORDLIFE is now the largest network of private cord blood banks in Asia Pacific with state-of-the-art cord-blood and tissue processing and cryopreservation facilities in the country.

Once considered a medical waste, the blood left in the umbilical cordthe part of the placenta that delivers nutrients to a fetusafter a baby is delivery is now known to be a rich source of blood-forming stem cells.

These cells have been found to be potentially useful in treating diseases that require stem cell transplants (also called bone marrow transplants) such as certain kinds of leukemia or lymphoma, aplastic anemia (a blood disorder in which the bodys bone marrow doesnt make enough new blood cells), severe sickle cell disease and severe combined immunodeficiency.

Unlike with bone marrow, which is obtained through a painful medical procedure, there is only one chance to collect this seemingly precious stuff: immediately after the babys birth.

This is why a number of expectant parents in the country are being offered a chance to save stem cells from their babys umbilical cord blood via what is known as cord-blood banking.

Safeguard

Cordlife Philippines medical director Arvin Faundo said: Its a type of safeguard because the genetically unique stem cells have current and potential uses in medical treatment. No parent wishes his/her child to experience the heartbreaking effects of any illness. What we at Cordlife offer them is the chance to prepare for potential eventualitiesto secure the future well-being and happiness of their family.

Cordlife Philippines is a subsidiary of Cordlife Group Ltd., a company listed on the Singapore Exchange. Launched in February 2010 as the Philippines first and only cord-blood processing and cryopreservation facility, its facility was ISO-certified and built in accordance to global gold standards such as the American Association of Blood Banks.

The 365-day facility, located within UP-Ayala Land TechnoHub in Quezon City, is equipped with the worlds most advanced fully automated cord-blood processing system, the Swiss-made Sepax.

CordLife uses the US FDA-approved cryogenic storage pouch.

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Freezing newborns own stem cells for possible future use

Knee Cartilage Repair With Tissue Engineered Scaffold To Hold Patient #39;s Own Stem Cells
Cartilage in the knee can get damaged by sporting injuries (different from wear and tear in the older patient). These injuries respond very well to stem cell procedures when coupled with tissue...

By: Orthopaedic Clinic, Singapore - Limb Salvage and Revision Arthroplasty Surgery Pte Ltd

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Knee Cartilage Repair With Tissue Engineered Scaffold To Hold Patient's Own Stem Cells - Video

CAMBRIDGE, England, Dec. 25 (UPI) -- The first time in history, researchers have successfully used human embryonic stem cells to create primordial germ cells, cells that divide and mature into egg and sperm. Previously, the feat had been accomplished using rodent stem cells -- not those from a human embryo.

"Researchers have been attempting to create human primordial germ cells (PGCs) in the petri dish for years," leader author Jacob Hanna, a researcher in the Institute's Molecular Genetics Department, said in a released statement.

Stem cells are undifferentiated biological cells capable of dividing and transforming into specialized cells. They are the most basic of biological building blocks.

"The creation of primordial germ cells is one of the earliest events during early mammalian development," study co-author Naoko Irie, researcher at the Wellcome Trust/Cancer Research UK Gurdon Institute at the University of Cambridge, said in a press release.

"It's a stage we've managed to recreate using stem cells from mice and rats, but until now few researches have done this systematically using human stem cells," Irie added.

Researchers say the newly realized feat has revealed differences between embryo development in humans and rodents -- discrepancies that could undermine studies that extrapolate mice and rat-based evidence to human-related conclusions.

"Having the ability to create human PGCs in the petri dish will enable us to investigate the process of differentiation on the molecular level," Hanna said.

The research was published this week in the journal Cell.

2014 United Press International, Inc. All Rights Reserved. Any reproduction, republication, redistribution and/or modification of any UPI content is expressly prohibited without UPI's prior written consent.

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Scientists create human primordial cells in the lab

An investigative panel under the government-backed Riken research institute announced Friday that the so-called STAP stem cells described in the research papers lead-authored by Haruko Obokata were created from embryonic stem (ES) cells.

It also said it discovered two more cases of research misconduct by the embattled scientist.

The panel concluded STAP stem cells . . . were derived from ES cells, based on examinations of the remaining samples, Isao Katsura, director general of the National Institute of Genetics and head of the seven-member panel, told reporters Friday in Tokyo.

Katsura also noted that the chimera mice and teratomas claimed to be developed from STAP cells were highly likely to be generated from ES cells.

However, the panel was unable to reach a conclusion on who introduced the embryonic stem cells, or whether they were introduced deliberately or by accident, citing insufficient evidence.

Moreover, the panel, which had been investigating the two papers on stimulus-triggered acquisition of pluripotency published in the British journal Nature, found two fresh instances of research misconduct by Obokata, in connection with data in one of the papers.

We concluded Obokata fabricated data for two charts on growth curves of (STAP stem) cells and DNA methylation, Katsura said.

The findings add to two counts of research misconduct found to have been committed by the 31-year-old biologist by another Riken panel earlier this year. This, along with other allegations of misconduct, prompted Riken to set up the panel headed by Katsura in September. Obokata resigned from the institute Sunday.

Meanwhile, Katsura said that Teruhiko Wakayama and Hitoshi Niwa, two of the co-authors of the STAP papers subject to the panels review, were not involved in any misconduct. He added that Yoshiki Sasai, another co-author who oversaw Obokatas writing, was not investigated because he committed suicide in August.

The Nature papers published in January claimed that the team of scientists led by Obokata found a groundbreaking method of stem cell generation, but they were retracted in July.

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STAP cells claimed by Obokata were likely embryonic stem cells

Scientists at the University of Cambridge working with the Weizmann Institute have created primordial germ cells - cells that will go on to become egg and sperm - using human embryonic stem cells. Although this had already been done using rodent stem cells, the study, published today in the journal Cell, is the first time this has been achieved efficiently using human stem cells.

When an egg cell is fertilised by a sperm, it begins to divide into a cluster of cells known as a blastocyst, the early stage of the embryo. Within this ball of cells, some cells form the inner cell mass - which will develop into the foetus - and some form the outer wall, which becomes the placenta. Cells in the inner cell mass are 'reset' to become stem cells - cells that have the potential to develop into any type of cell within the body. A small number of these cells become primordial germ cells (PGCs) - these have the potential to become germ cells (sperm and egg), which in later life will pass on the offspring's genetic information to its own offspring.

"The creation of primordial germ cells is one of the earliest events during early mammalian development," says Dr Naoko Irie, first author of the paper from the Wellcome Trust/Cancer Research UK Gurdon Institute at the University of Cambridge. "It's a stage we've managed to recreate using stem cells from mice and rats, but until now few researches have done this systematically using human stem cells. It has highlighted important differences between embryo development in humans and rodents that may mean findings in mice and rats may not be directly extrapolated to humans."

Professor Surani at the Gurdon Institute, who led the research, and his colleagues found that a gene known as SOX17 is critical for directing human stem cells to become PGCs (a stage known as 'specification'). This was a surprise as the mouse equivalent of this gene is not involved in the process, suggesting a key difference between mouse and human development. SOX17 had previously been shown to be involved in directing stem cells to become endodermal cells, which then develop into cells including those for the lung, gut and pancreas, but this is the first time it has been seen in PGC specification.

The group showed that PGCs could also be made from reprogrammed adult cells, such as skin cells, which will allow investigations on patient-specific cells to advance knowledge of the human germline, infertility and germ cell tumours. The research also has potential implications for understanding the process of 'epigenetic' inheritance. Scientists have known for some time that our environment - for example, our diet or smoking habits - can affect our genes through a process known as methylation whereby molecules attach themselves to our DNA, acting like dimmer switches to increase or decrease the activity of genes. These methylation patterns can be passed down to the offspring.

Professor Surani and colleagues have shown that during the PGC specification stage, a programme is initiated to erase these methylation patterns, acting as a 'reset' switch. However, traces of these patterns might be inherited - it is not yet clear why this might occur.

"Germ cells are 'immortal' in the sense that they provide an enduring link between all generations, carrying genetic information from one generation to the next," adds Professor Surani. "The comprehensive erasure of epigenetic information ensures that most, if not all, epigenetic mutations are erased, which promotes 'rejuvenation' of the lineage and allows it to give rise to endless generations. These mechanisms are of wider interest towards understanding age-related diseases, which in part might be due to cumulative epigenetic mutations."

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The above story is based on materials provided by University of Cambridge. The original story is licensed under a Creative Commons Licence. Note: Materials may be edited for content and length.

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Egg and sperm race: Scientists create precursors to human egg and sperm

Southern Illinois University/Science photo Library

Some hope that sperm cells could one day be derived from the skin cells of a man who is otherwise sterile and that a similar process cold produce viable egg cells from a sterile woman's body.

Israeli and UK researchers have created human sperm and egg precursor cells in a dish, starting from a person's skin cells. The achievement is a small step towards a treatment for infertility, although one that could face significant controversy and regulatory hurdles.

The experiment, reported online in Cell on 24 December1, recreates in humans parts of a procedure first developed in mice, in which cells called induced pluripotent stem (iPS) cells reprogrammed cells that can differentiate into almost any cell type are used to create sperm or eggs that are subsequently manipulated to produce live births by in vitro fertilization.

In 2012, stem-cell biologist Mitinori Saitou of Kyoto University in Japan and his collaborators created the first artificial primordial germ cells (PGCs)2. These are specialized cells that emerge during embryonic development and later give rise to sperm or eggs. Saitou made them in a dish, starting with skin cells reprogrammed to an embryonic-like state through iPS-cell technology (see 'Stem cells: Egg engineers'). They also were able to achieve the same result starting with embryonic stem cells.

Although his cells could not develop beyond this precursor stage in the dish, Saito found that if he placed them in mouse testes, they would mature into sperm, and if he placed them in ovaries, they would mature into functional eggs. Both sperm and eggs could be used for in vitro fertilization.

Efforts to engineer similarly functional gametes in humans have produced PGC-like cells, but with such a low efficiency success rate of turning stem cells into gametes that it was difficult for others to expand on the work.. Previous efforts also required the introduction of genes that would render the cells unusable in the clinic.

Ewen Callaway reports on the ethical challenges of using lab-made sperm and egg cells in fertility treatments.

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Now a team led by Azim Surani of the University of Cambridge, UK, and Jacob Hanna of the Weizmann Institute of Science in Rehovot, Israel, has replicated the in vitro portion the first half, says Hanna of Saitous efforts in humans.

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Rudimentary egg and sperm cells made from stem cells

Physician-scientists at OHSU Doernbecher Children's Hospital reveal a high-fat diet and obesity during pregnancy compromise the blood-forming, or hematopoietic, stem cell system in the fetal liver responsible for creating and sustaining lifelong blood and immune system function.

The life-long burden of a western-style diet on the heart and circulatory system have long been appreciated. However, prior to this study, no one had considered whether the developing blood stem cells might be similarly vulnerable to prenatal high-fat diet and/or maternal obesity. The findings are published in the journal Molecular Metabolism.

"Our results offer a model for testing whether the effects of a high-fat diet and obesity can be repaired through dietary intervention, a key question when extrapolating this data to human populations," said Daniel L. Marks, M.D., Ph.D., co-investigator and professor of pediatric endocrinology in the OHSU School of Medicine and Pap Family Pediatric Research Institute at OHSU Doernbecher Children's Hospital.

Several years ago, Marks and colleagues developed a mouse model that closely mimics the high-fat, high-simple-sugar diet currently consumed by many young women of childbearing age. Their subsequent research demonstrated that maternal overnutrition in mice significantly reduced the size of the fetal liver.

Armed with this information, Marks partnered with another stem cell expert, Peter Kurre, M.D., co-investigator on the current study and professor of pediatric oncology in the OHSU School of Medicine and the Pap Family Pediatric Research Institute at OHSU Doernbecher Children's Hospital.

Together, they discovered that the complex changes that occur as a result of maternal high-fat diet and obesity put significant constraints on the growth and expansion of blood stem cells in the fetal liver, which ultimately compromises the developing immune system.

"In light of the spreading western-style, high-fat diet and accompanying obesity epidemic, this study highlights the need to better understand the previous unrecognized susceptibility of the stem and progenitor cell system," Kurre said. "These findings may provide broad context for the rise in immune disease and allergic disposition in children."

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High-fat diet, obesity during pregnancy harms stem cells in developing fetus

Scientists have made primitive forms of artificial sperm and eggs in a medical feat that could transform the understanding of age-related diseases and fertility problems.

Researchers in Cambridge made the early-stage sex cells by culturing human embryonic stem cells under carefully-controlled conditions for a week.

They followed the success by showing that the same procedure can convert adult skin tissue into precursors for sperm and eggs, raising the prospect of making sex cells that are genetically matched to patients.

The cells should have the potential to grow into mature sperm and eggs, though this has never been done in the lab before. The next step for the researchers will be to inject the cells into mouse ovaries or testes to see if they fully develop in the animals.

British law prohibits fertility clinics in the UK from using artificial sperm and eggs to treat infertile couples. But if the law was revised, skin cells could potentially be taken from patients and turned into genetically identical sperm or eggs for use in IVF therapies.

Skin cells from a woman could only be used to make eggs because they lack the Y chromosome. Those from a male might theoretically be turned into eggs as well as sperm, but Azim Surani, who led the work at the Gurdon Institute in Cambridge, said that on the basis of current knowledge, that was unlikely.

Its not impossible that we could take these cells on towards making gametes, but whether we could ever use them is another question for another time, Surani told the Guardian.

Researchers have made sperm and eggs from rodent stem cells before but have struggled do the same with human cells. In 2012, Japanese scientists created mouse eggs from stem cells and used them to make baby mice. Three years earlier, scientists at Newcastle University claimed to have made human sperm from stem cells, but their scientific paper was retracted amid allegations of plagiarism. In 2002, US researchers produced male and female mouse pups from male stem cells.

Suranis team tried a number of different approaches before hitting on a culture process that turned up to half of the human stem cells in the dish into precursors of sperm and eggs. Over the five day process, the scientists added natural chemicals called growth factors to nudge the cells in the right developmental direction.

Its remarkably fast. We can now take any embryonic stem cell line and once we have them in the proper conditions, we can make these primordial cells in five to six days, Surani said. Details of the work, a collaboration with the Weizmann Institute in Israel, are published in the journal, Cell.

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Scientists use skin cells to create artificial sperm and eggs