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Cell and signaling pathway that regulates the placental blood stem cell niche identified

By adminMarch 2, 2012Stem Cell Treatment

ScienceDaily (Mar. 1, 2012) UCLA stem cell researchers have discovered a critical placental niche cell and signaling pathway that prevent blood precursors from premature differentiation in the placenta, a process necessary for ensuring proper blood supply for an individual's lifetime.

The placental niche, a stem cell "safe zone," supports blood stem cell generation and expansion without promoting differentiation into mature blood cells, allowing the establishment of a pool of precursor cells that provide blood cells for later fetal and post-natal life, said study senior author Dr. Hanna Mikkola, an associate professor of molecular cell and developmental biology and a researcher at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Mikkola and her team found that PDGF-B signaling in trophoblasts, specialized cells of the placenta that facilitate embryo implantation and gas and nutrient exchanges between mother and fetus, is vital to maintaining the unique microenvironment needed for the blood precursors. When PDGF-B signaling is halted, the blood precursors differentiate prematurely, creating red blood cells in the placenta, Mikkola said.

The study, done in mouse models, appears March 1, 2012, in the peer-reviewed journal Developmental Cell.

"We had previously discovered that the placenta provides a home for a large supply of blood stem cells that are maintained in an undifferentiated state. We now found that, by switching off one signaling pathway, the blood precursors in the placenta start to differentiate into red blood cells," Mikkola said. "We learned that the trophoblasts act as powerful signaling centers that govern the niche safe zone."

The study found that the PDGF-B signaling in the trophoblasts is suppressing production of Erythropoietin (EPO), a cytokine that controls red blood cell differentiation.

"When PDGF-B signaling is lost, excessive amounts of EPO are produced in the placenta, which triggers differentiation of red blood cells in the placental vasculature," said Akanksha Chhabra, study first author and a post-doctoral fellow in Mikkola's lab.

Mikkola and Chhabra used mouse models in which the placental structure was disrupted so they could observe what cells and signaling pathways were important components of the niche.

"The idea was, if we mess up the home where the blood stem cells live, how do these cells respond to the altered environment," Chhabra said. "We found that it was important to suppress EPO where blood stem cell expansion is desired and to restrict its expression to areas where red blood cell differentiation should occur."

The finding, Chhabra said, was exciting in that one single molecular change "was enough to change the function of an important blood stem cell niche."

UGA study reveals basic molecular 'wiring' of stem cells

By adminMarch 1, 2012Stem Cell Medicine

Public release date: 1-Mar-2012 [ | E-mail | Share ]

Contact: Stephen Dalton sdalton@uga.edu 706-542-9857 University of Georgia

Athens, Ga. Despite the promise associated with the therapeutic use of human stem cells, a complete understanding of the mechanisms that control the fundamental question of whether a stem cell becomes a specific cell type within the body or remains a stem cell hasuntil noweluded scientists.

A University of Georgia study published in the March 2 edition of the journal Cell Stem Cell, however, creates the first ever blueprint of how stem cells are wired to respond to the external signaling molecules to which they are constantly exposed. The finding, which reconciles years of conflicting results from labs across the world, gives scientists the ability to precisely control the development, or differentiation, of stem cells into specific cell types.

"We can use the information from this study as an instruction book to control the behavior of stem cells," said lead author Stephen Dalton, Georgia Research Alliance Eminent Scholar of Molecular Biology and professor of cellular biology in the UGA Franklin College of Arts and Sciences. "We'll be able to allow them to differentiate into therapeutic cell types much more efficiently and in a far more controlled manner."

The previous paradigm held that individual signaling molecules acted alone to set off a linear chain of events that control the fate of cells. Dalton's study, on the other hand, reveals that a complex interplay of several molecules controls the "switch" that determines whether a stem cell stays in its undifferentiated state or goes on to become a specific cell type, such as a heart, brain or pancreatic cell.

"This work addresses one of the biggest challenges in stem cell researchfiguring out how to direct a stem cell toward becoming a specific cell type," said Marion Zatz, who oversees stem cell biology grants at the National Institutes of Health's National Institute of General Medical Sciences, which partially supported the work.

"In this paper, Dr. Dalton puts together several pieces of the puzzle and offers a model for understanding how multiple signaling pathways coordinate to steer a stem cell toward differentiating into a particular type of cell. This framework ultimately should not only advance a fundamental understanding of embryonic development, but facilitate the use of stem cells in regenerative medicine."

To get a sense of how murky the understanding of stem cell differentiation was, consider that previous studies reached opposite conclusions about the role of a common signaling molecule known as Wnt. About half the published studies found that Wnt kept a molecular switch in an "off" position, which kept the stem cell in its undifferentiated, or pluripotent, state. The other half reached the opposite conclusion.

Could the same Wnt molecule be responsible for both outcomes? As it turns out, the answer is yes. Dalton's team found that in small amounts, Wnt signaling keeps the stem cell in its pluripotent state. In larger quantities, it does the opposite and encourages the cell to differentiate.

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UGA study reveals basic molecular 'wiring' of stem cells

Factbox: Neurotechnologies in spotlight of UK ethics review

By adminMarch 1, 2012Uncategorized

LONDON (Reuters) - Britain's Nuffield Council on Bioethics, which examines ethical issues raised by new developments in biology and medicine, launched a consultation on Thursday on the ethics of new technologies and devices that intervene in the human brain.

The three main areas of the group's focus are brain-computer interfaces, neurostimulation and neural stem cell therapy.

Here are some details about each area of research and how it is being explored.

* Brain computer interfaces (BCIs)

BCIs measure and analyze a person's brain signals and convert them into an output such as movement.

A paralyzed person, for example, could use a BCI to operate a wheelchair, or someone who has extreme difficulty speaking could use a BCI to communicate via a computer voice.

These sorts of applications have been shown to be successful in a few reported cases, but the technology has not yet been developed for regular clinical use and there are questions over whether these technologies are reliable enough for use in everyday life.

Military applications, such as remote control of vehicles and machinery are not yet in wide use but are being researched and tested, mainly in the United States.

Some commercial BCI developments are already on the market in the gaming sector. Gamers can buy a wireless headset that aims to replace a joystick by controlling game play through brain signals.

The use of BCIs sometimes require surgery to implant electrodes into a person's brain, although the most successful current developments are less invasive ones That detect brain signals from the scalp.

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Factbox: Neurotechnologies in spotlight of UK ethics review

UCLA scientists identify crucial cell and signaling pathway in placental blood stem cell niche

By adminMarch 1, 2012Uncategorized

Public release date: 1-Mar-2012 [ | E-mail | Share ]

Contact: Kim Irwin kirwin@mednet.ucla.edu 310-206-2805 University of California - Los Angeles Health Sciences

UCLA stem cell researchers have discovered a critical placental niche cell and signaling pathway that prevent blood precursors from premature differentiation in the placenta, a process necessary for ensuring proper blood supply for an individual's lifetime.

The study, done in mouse models, appears March 1, 2012, in the peer-reviewed journal Developmental Cell.

The study found that the PDGF-B signaling in the trophoblasts is suppressing production of Erythropoietin (EPO), a cytokine that controls red blood cell differentiation.

Mikkola and Chhabra used mouse models in which the placental structure was disrupted so they could observe what cells and signaling pathways were important components of the niche.

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UCLA scientists identify crucial cell and signaling pathway in placental blood stem cell niche

Ethan Zohn Undergoes Stem-Cell Transplant

By adminMarch 1, 2012Stem Cell Doctors

Ethan Zohn

Courtesy Jenna Morasca

"Ethan asked the doctor what was the record time for getting out of here, so he wants to beat that," Zohn's longtime girlfriend Jenna Morasca, who is staying with him at the hospital, tells PEOPLE.

"His doctor said there was no prize, and Ethan said, 'Yes, there is. You're going to tell the other patients that I made it out in three weeks.' "

Returning to the same ward where they stayed two years ago when Zohn was first diagnosed was difficult for the couple.

"No one wants to come back here. Even though the nurses and doctors are wonderful, this is one place where you really don't want to see anybody ever again," Morasca says. "Then starting the chemo and being attached to a pump that you're going to be attached to for the next three to five weeks made it very real."

On a happier note, Morasca says the support they've received from around the world has made all the difference. With help from family and friends, she was able to duck out of the hospital [Monday] to shoot the first episode of her new show, Fitness Guinea Pigs, which will air on YouTube's news channel.

And though Zohn's immune system is weakened, he can routinely have healthy visitors to his room, which he refers to as his "bubble." The two even created the Twitter account @Ethansbubble, which their friends can access to pen comical perspectives on the experience.

"We don't know who is actually writing the Tweets, so it makes it really fun," says Morasca. "It's all about thinking positively."

After the transplant, doctors will watch to make sure Zohn's body accepts the new stem-cells before releasing him from the hospital. Until then, the couple is making the best of their close quarters.

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Ethan Zohn Undergoes Stem-Cell Transplant

'Survivor''s Ethan Zohn Gets Stem Cell Transplant

By adminMarch 1, 2012Stem Cell Doctors

Survivor winner Ethan Zohn underwent a stem-cell transplant on Wednesday from one of his brothers in his continuing battle with Hodgkin's lymphoma.

Ethan's longtime girlfriend Jenna Morasca, who is staying with him in the hospital, tells People.com that they had returned to the same ward where they stayed when Zohn was first diagnosed two years ago. "No one wants to come back here," Jenna said. "Even though the nurses and doctors are wonderful, this is one place where you really don't want to see anybody ever again."

Survivor Winner Ethan Zohn's Cancer Returns

Jenna said this time around, Ethan asked the doctor what was the record time was "for getting out" and that he wanted to beat whatever that is. "His doctor said there was no prize, and Ethan said, 'Yes, there is. You're going to tell the other patients that I made it out in three weeks.'" Doctors will be closely watching Ethan to make sure his body accepts the new stem cells before he is released.

Jenna says for now the two are making the best of their close quarters. "I actually really like it, because he can't escape me," she tells People. "He's forced to be around me all the time and listen to everything I say. I'm like, 'What do you think of this hair?' and 'What about this lipstick color?' And he's over there pressing the pain medication pump button."

Cancer Survivor Ethan Zohn Stands Up to Cancer

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'Survivor''s Ethan Zohn Gets Stem Cell Transplant

'Survivor's' Zohn gets a stem-cell transplant

By adminMarch 1, 2012Stem Cell Doctors

By Josh Grossberg, E! Online

Forget feeling like a million bucks. Ethan Zohn is feeling like a new man.

The "Survivor: Africa" champ underwent a stem-cell transplant Wednesday to treat a recurrence of his Hodgkin's lymphoma cancer--and he has his brother to thank for the immuno-boost.

Outwit, outlast, outplay has never quite meant so much.

More from E: Ethan Zohn and Jenna Morasca dye their hair pink to raise awareness for World Cancer Day

"Today I leap into a healthy new body. Today is the start of the rest of my life. Thank You to my bro Lee &all who have supported me. Love!" the reality star tweeted presumably before undergoing the transfusion.

And of course, Jenna Morasca, Zohn's girlfriend and winner of "Survivor: The Amazon," was right there with him the whole time.

"Thanks @JennaMorasca for being by my side. Love you," he added in a follow up.

Just before the transplant, Morasca wrote on Twitter: "Today @EthanZohn gets new stem cells &new cancer free life FOREVER! And we get our lives back. Send positive healing vibes #getbetterethan"

More from E: 'Survivor' Ethan Zohn's cancer returns

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'Survivor's' Zohn gets a stem-cell transplant

A*STAR Scientists Make Groundbreaking Discovery on Stem Cell Regulation

By adminMarch 1, 2012Stem Cell Medicine

Embryonic stem cells hold great potential for the development of cellular therapies, where stem cells are used to repair tissue damaged by disease or trauma. This is due to their unique ability to renew themselves and differentiate into any specific types of cell in the body. One of the challenges with cellular therapies is ensuring that ESCs are fully and efficiently differentiated into the correct cell type. This study sheds light on understanding how ESCs are regulated, which is essential to overcome these challenges and turn the vision of cell therapies into reality.

Using a mouse model, the team of scientists from IMB showed that high levels of Amd1 , a key enzyme in the polyamine synthesis pathway, is essential for maintenance of the ESC state and self renewal of ESCs. To further demonstrate the critical role of Amd1 in ESC self-renewal, the scientists showed that increasing Amd1 levels led to delayed ESC differentiation. The research also revealed that downregulation of Amd1 was necessary for differentiation of ESCs into neural precursor cells and that Amd1 is translationally regulated by a micro-RNA (miRNA), the first ever demonstration of miRNA-mediated regulation of the polyamine pathway.

While the polyamine pathway is well established and polyamines are known to be important in cancer and cell proliferation, their role in ESC regulation until now was unknown. This novel discovery, linking polyamine regulation to ESC biology, came about when the team set up a genome-wide screen to look for mRNAs under translational control in order to identify new regulators of ESC differentiation to neural precursor cells.

Dr Leah Vardy, Principle Investigator at the IMB and lead author of the paper, said, "The polyamines that Amd1 regulate have the potential to regulate many different aspects of self renewal and differentiation. The next step is to understand in more detail the molecular targets of these polyamines both in embryonic stem cells and cells differentiating to different cellular lineages. It is possible that manipulation of polyamine levels in embryonic stem cells through inhibitors or activators of the pathway could help direct the differentiation of embryonic stem cells to more clinically useful cell types."

Prof. Birgitte Lane, Executive Director of IMB, said, "This is a fine piece of fundamental research that will have breakthrough consequences in many areas and can bring about far-reaching applications. Developing cellular therapies is just one long-term clinical benefit of understanding ESC biology, which can also help develop stem cell systems for disease modeling, developing new drugs as well as a tool for researchers to answer other biological questions."

Notes for editors: The research findings can be found in the 1st March issue of Genes and Development under the title, "AMD1 is essential for ESC self-renewal and is translationally down-regulated on differentiation to neural precursor cells" by Dawei Zhang (1,4), Tianyun Zhao (1,4), Haw Siang Ang (2), Peini Chong (1), Ryotaro Saiki (3), Kazuei Igarashi (3), Henry Yang (2), and Leah A. Vardy (1,5).

1. Institute of Medical Biology, A*STAR, Singapore 2. Cancer Science Institute, National University of Singapore 3. Graduate School of Pharmaceutical Sciences, Chiba University, Japan 4. These authors contributed equally to this work 5. Corresponding author

About the Institute of Medical Biology (IMB)

IMB is one of the Biomedical Sciences Institutes of the Agency for Science, Technology and Research (A*STAR). It was formed in 2007, the 7th and youngest of the BMRC Research Institutes, with a mission to study mechanisms of human disease in order to discover new and effective therapeutic strategies for improved quality of life.

IMB hosts 20 research teams of international excellence in stem cells, genetic diseases, cancer and skin and epithelial biology, and works closely with clinical collaborators to target the challenging interface between basic science and clinical medicine. Its growing portfolio of strategic research topics is targeted at translational research on the mechanisms of human diseases, with a cell-to-tissue emphasis that can help identify new therapeutic strategies for disease amelioration, cure and eradication.

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A*STAR Scientists Make Groundbreaking Discovery on Stem Cell Regulation

:: 01, Mar 2012 :: A*STAR SCIENTISTS MAKE GROUNDBREAKING DISCOVERY ON STEM CELL REGULATION

By adminMarch 1, 2012Stem Cell Clinic

MEDIA RELEASE

A*STAR Scientists Make Groundbreaking Discovery on Stem Cell Regulation

New link between polyamine levels and embryonic stem cell state deepens our understanding of embryonic stem cell regulation which is a key step in bringing cellular therapies from the laboratory to the clinic.

1. A*STAR scientists have for the first time, identified that precise regulation of polyamine[1] levels is critical for embryonic stem cell (ESC) self-renewal the ability of ESCs to divide indefinitely and directed differentiation. This paper is crucial for better understanding of ESC regulation and was published in the journal Genes & Development on 1st March by the team of scientists from the Institute of Medical Biology (IMB), a research institute under the Agency for Science, Technology and Research (A*STAR).

2. Embryonic stem cells hold great potential for the development of cellular therapies, where stem cells are used to repair tissue damaged by disease or trauma. This is due to their unique ability to renew themselves and differentiate into any specific types of cell in the body. One of the challenges with cellular therapies is ensuring that ESCs are fully and efficiently differentiated into the correct cell type. This study sheds light on understanding how ESCs are regulated, which is essential to overcome these challenges and turn the vision of cell therapies into reality.

3. Using a mouse model, the team of scientists from IMB showed that high levels of Amd1[2], a key enzyme in the polyamine synthesis pathway, is essential for maintenance of the ESC state and self renewal of ESCs. To further demonstrate the critical role of Amd1 in ESC self-renewal, the scientists showed that increasing Amd1 levels led to delayed ESC differentiation. The research also revealed that downregulation of Amd1 was necessary for differentiation of ESCs into neural precursor cells and that Amd1 is translationally regulated by a micro-RNA (miRNA), the first ever demonstration of miRNA-mediated regulation of the polyamine pathway.

4. While the polyamine pathway is well established and polyamines are known to be important in cancer and cell proliferation, their role in ESC regulation until now was unknown. This novel discovery, linking polyamine regulation to ESC biology, came about when the team set up a genome-wide screen to look for mRNAs under translational control in order to identify new regulators of ESC differentiation to neural precursor cells.

6. Dr Leah Vardy, Principle Investigator at the IMB and lead author of the paper, said, The polyamines that Amd1 regulate have the potential to regulate many different aspects of self renewal and differentiation. The next step is to understand in more detail the molecular targets of these polyamines both in embryonic stem cells and cells differentiating to different cellular lineages. It is possible that manipulation of polyamine levels in embryonic stem cells through inhibitors or activators of the pathway could help direct the differentiation of embryonic stem cells to more clinically useful cell types.

7. Prof. Birgitte Lane, Executive Director of IMB, said, This is a fine piece of fundamental research that will have breakthrough consequences in many areas and can bring about far-reaching applications. Developing cellular therapies is just one long-term clinical benefit of understanding ESC biology, which can also help develop stem cell systems for disease modeling, developing new drugs as well as a tool for researchers to answer other biological questions.

Notes for editor:

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:: 01, Mar 2012 :: A*STAR SCIENTISTS MAKE GROUNDBREAKING DISCOVERY ON STEM CELL REGULATION

Meet Cord Blood Registry’s Leader of Laboratory Operations – Video

By adminMarch 1, 2012Uncategorized

28-02-2012 16:31 Learn more about cord blood stem cells here http://www.cordblood.com Cord Blood Registry takes pride in leading the cord blood banking industry with its state-of-the-art lab. Meet Kristen, who leads the effort to make sure we're providing our clients with the best once their babies' stem cells arrive in Tucson. Kristen is one of the many people who make sure that, from that first phone call to the day your baby's stem cells are collected and stored, you receive the industry's best service and support. For more information on CBR's processes, visit: http://www.cordblood.com

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Meet Cord Blood Registry's Leader of Laboratory Operations - Video