Stem Cell Clinic

UCLA Scientists Identify Cell and Signaling Pathway that Regulates the Placental Blood Stem Cell Niche

By Uncategorized

Newswise 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 individuals 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 Mikkolas 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.

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UCLA Scientists Identify Cell and Signaling Pathway that Regulates the Placental Blood Stem Cell Niche

Advanced Cell Technology Announces 2011 Financial Results

By Uncategorized

MARLBOROUGH, Mass.--(BUSINESS WIRE)--

Advanced Cell Technology, Inc. (ACT, OTCBB: ACTC), a leader in the field of regenerative medicine, today announced year-end results for the year ended December 31, 2011. The Company utilized $13.6 million in cash for operations during the year, compared to $8.8 million in the year-earlier period. The increase in cash utilization resulted primarily from ACTs ongoing clinical activities in the US and Europe. ACT ended the year with cash and cash equivalents of $13.1 million, compared to $15.9 million in cash and cash equivalents in the year-earlier period.

Some of the 2011 highlights included:

2011 was a very important and successful year for ACT as we began our Phase 1/2 trials for the treatment of macular degeneration, said Gary Rabin, chairman and CEO of ACT. We are very excited about the preliminary Phase 1/2 clinical data from our dry-AMD and Stargardts disease trials, which were published in The Lancet earlier this year. The data demonstrated the safety of ACTs human embryonic stem cell (hESC)-derived retinal pigment epithelium (RPE) cells for the treatment of both diseases. The vision of both patients appears to have improved after transplantation, and no adverse safety issues have been observed. We look forward to validating these early findings as we expand these clinical activities throughout this year. Additionally, we made significant progress in advancing our scientific platform, expanding our board of directors and management team and strengthening our balance sheet.

The Company also announced today that it expects to shortly file a preliminary proxy statement with the Securities and Exchange Commission in which it will seek shareholder approval for a reverse split of between 1-for 20 and 1-for 80 shares. The Company is pursuing the reverse split for the sole purpose of meeting the requirements necessary for a listing on the Nasdaq Global Market. The Company believes that a listing on a national change will allow it to expand its shareholder base and improve the marketability of its common stock by attracting a broader range of investors.

Conference Call

The Company will hold a conference call at 9:00 a.m. EST tomorrow, during which it will discuss 2011 results and provide an update on clinical activities. Interested parties should dial (888)264-3177 followed by the reference conference ID number: 57426004. The call will be available live and for replay by webcast at: http://us.meeting-stream.com/advancedcelltechnology030212

About Advanced Cell Technology, Inc.

Advanced Cell Technology, Inc., is a biotechnology company applying cellular technology in the field of regenerative medicine. For more information, visitwww.advancedcell.com.

Forward-Looking Statements

Link:
Advanced Cell Technology Announces 2011 Financial Results

Groundbreaking discovery on stem cell regulation

By Stem Cell Treatment

ScienceDaily (Mar. 1, 2012) 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).

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[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.

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."

Notes:

[1] Polyamines are required for a wide range of cellular processes, including differentiation and cell proliferation, and their levels are tightly regulated.

[2] Amd1 (Adenosyl methionine decarboxylase) is a critical enzme required for the synthesis of the polyamines spermine and spermidine.

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Groundbreaking discovery on stem cell regulation

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

By Stem 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."

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

UGA study reveals basic molecular 'wiring' of stem cells

By Stem 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.

More here:
UGA study reveals basic molecular 'wiring' of stem cells

Factbox: Neurotechnologies in spotlight of UK ethics review

By Uncategorized

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.

Continued here:
Factbox: Neurotechnologies in spotlight of UK ethics review

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

By Uncategorized

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 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.

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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 Stem 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 Stem 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

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