Category Archives: Stem Cell Research

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

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

BEVERLY, MA and TORONTO--(Marketwire -03/01/12)- Hamilton Thorne Ltd. (TSX-V: HTL.V - News), a leading provider of precision laser devices and advanced imaging systems for the fertility, stem cell and developmental biology research markets, today announced the expansion of its distribution partnership with Leica Microsystems GmbH of Wetzlar, Germany, a leading global producer of innovative high-tech precision optics systems for the analysis of microstructures. This new arrangement will provide Leica Microsystems with access to Hamilton Thorne's current portfolio of laser products, as well as select pipeline products including the strongly anticipated IMSI STRICT software for the fertility market.

The expanded partnership will enable Hamilton Thorne and Leica Microsystems to further penetrate markets that have proven successful and synergistic for both companies such as fertility and cell research markets. The new multi-year agreement provides Leica Microsystems with non-exclusive rights to market and distribute Hamilton Thorne products in Spain, Portugal and Italy, in addition to the North American market. Hamilton Thorne and Leica Microsystems continue to collaborate on technical product integration between the two companies.

"We are pleased to continue our strategic partnership with Leica Microsystems, a renowned global leader in microscopy and optics. In the US markets especially, Leica Microsystems has provided Hamilton Thorne with significant technical advantages, which has enabled our internal sales team to enter new and beneficial developmental biology research markets," says David Wolf, President and Chief Executive Officer of Hamilton Thorne. "Hamilton Thorne has launched several game-changing products in 2011, like our new LYKOS laser system, and will continue to introduce new and innovative products in 2012. The renewed partnership with Leica Microsystems will expand the distribution channels for these new products in North America and Europe, and help drive rapid product adoption."

"During the course of our partnership, Hamilton Thorne's products have proven to be an ideal extension to our robust catalog of optics systems, and we are confident that our expanded relationship will continue to positively contribute to the bottom line of both companies," says Sebastian Tille, Head of Business Segment 'Widefield Imaging', Life Science Division of Leica Microsystems. "Hamilton Thorne's laser products offer our current customers best-in-class cell analysis capabilities, and with our combined strengths, we can further penetrate and open up new sales opportunities in areas such as advanced cell biology."

The expansion of the existing strategic relationship will continue to focus on joint product development, manufacturing of select components for Hamilton Thorne products, and distribution arrangements in additional markets.

About Leica Microsystems (www.leica-microsystems.com) Leica Microsystems is a world leader in microscopes and scientific instruments. Founded as a family business in the nineteenth century, the company's history was marked by unparalleled innovation on its way to becoming a global enterprise.

Its historically close cooperation with the scientific community is the key to Leica Microsystems' tradition of innovation, which draws on users' ideas and creates solutions tailored to their requirements. At the global level, Leica Microsystems is organized in four divisions, all of which are among the leaders in their respective fields: the Life Science Division, Industry Division, Biosystems Division and Medical Division.

Leica Microsystems' Biosystems Division, also known as Leica Biosystems, offers histopathology laboratories the most extensive product range with appropriate products for each work step in histology and for a high level of productivity in the working processes of the entire laboratory.

The company is represented in over 100 countries with 12 manufacturing facilities in 7 countries, sales and service organizations in 19 countries and an international network of dealers. The company is headquartered in Wetzlar, Germany.

About Hamilton Thorne Ltd. (www.hamiltonthorne.com)

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Hamilton Thorne Expands Distribution Partnership With Leading Microscope and Optical Systems Producer Leica Microsystems

Research on preventing breast cancer recurrence, using organ regeneration to combat obesity-related diseases, and enabling vascular repair for patients suffering from cardiovascular disease has received awards at the ongoing Qatar International Conference on Stem Cell Science and Policy 2012. The award ceremony hosted by Qatar Foundation for Education, Science and Community Development at Qatar National Convention Centre recognised two professional researchers and one student researcher for excellence in stem cell research, with the research exhibited through poster presentations during the conference. Leaders from QF and top figures in the stem cell science and ethics field congratulated the award recipients. Dr Abdelali Haoudi, vice president for research at QF, said: We are truly impressed with the research presented this year in poster presentations, as well as in the oral presentations and panel discussions taking place throughout the conference. He added: Through this conference, we hope to drive further exploration in this field that will lead to even greater progress in applying stem cell science to prevent and treat diseases afflicting communities both in Qatar and around the world. The three posters were selected for recognition by a review committee, comprised of academics, researchers and scientists, including Nobel Laureates and international experts. Pegah Ghiabi, a researcher at the Stem Cell & Microenvironment Laboratory at Weill Cornell Medical College in Qatar, received an award for her poster presentation on research into therapy to inhibit the cancer stem cell population to prevent the recurrence of breast cancer. Research by Lara Bou-Khzam of the McGill University Health Centre Research Institute in Montreal, Canada, also received recognition. The poster focused on her stem cell research towards vascular repair for patients suffering from cardiovascular disease, one of the worlds leading causes of mortality. The final award was presented to Dr Heba al-Siddiqui for her research at the Harvard Stem Cell Institute on preventing chronic obesity-related diseases through tissue engineering and organ regeneration. Dr al-Siddiqui is a trainee in the Qatar Science Leadership Programme, a QF initiative aimed at equipping rising Qatari generations for leading roles in the countrys scientific and research endeavours. The Qatar International Conference on Stem Cell Science and Policy, organised through a partnership between QF and the James A. Baker III Institute of Public Policy at Rice University, will conclude today. The four-day conference, which featured expert panels and presentations on the latest opportunities and challenges in stem cell research, was attended by top figures in the fields of science, ethics and policy of stem cell research from across the Middle East region and around the world.

Continued here:
QF honours stem cell researchers

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

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.

More information: The research findings described in this news release can be found in the 29 Feb 2012 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, et al.

Provided by Agency for Science Technology and Research (A*STAR)

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Scientists make groundbreaking discovery on stem cell regulation

Women may make new eggs throughout their reproductive yearschallenging a longstanding tenet that females are born with finite supplies, a new study says. The discovery may also lead to new avenues for improving women's health and fertility.

A woman has two ovaries, which release eggs during her monthly ovulation.(Learn more about the human body.)

Previous research had suggested that a woman is born with all the egg cells she will ever have in her lifetime.

But in recent experiments, scientists discovered a new type of stem cell in the ovaries thatwhen grown in the labgenerates immature egg cells.The same immature cells isolated from adult mouse ovaries canturn into fertile eggs.

Stem cells,found in embryos and certain adult body tissues, have the potential to grow into many different types of cells.

(See"Liposuction Fat Turned Into Stem Cells, Study Says.")

The finding reinforces the team's previous experiments in mice, which had identified a new type of ovarian stem cell that renews a female mouse's source of eggs throughout its fertile years.

That study, published in the journal Nature in 2004, was the "first to reach the conclusion that this long-held belief in our fieldthat young girls are given a bank account at birth that you can no longer deposit eggs to, just withdraw fromwas no longer true," said study leaderJonathan Tilly.

By reinforcing these earlier results in people, the new study is a "big step forward" from the mouse work, emphasized Tilly, director of the Vincent Center for Reproductive Biology at Massachusetts General Hospital in Boston.

From a purely biological perspective, the concept that a woman would continually generate new eggs during her reproductive years makes sensesince men constantly replenish their sperm, Tilly added. (Read how men produce 1,500 sperm a second.)

Excerpt from:
Women Can Make New Eggs After All, Stem-Cell Study Hints

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.

Go here to see the original:
UCLA scientists identify crucial cell and signaling pathway in placental blood stem cell niche

Public release date: 29-Feb-2012 [ | E-mail | Share ]

Contact: Ong Siok Ming ong_siok_ming@a-star.edu.sg 65-682-66254 Agency for Science, Technology and Research (A*STAR), Singapore

A*STAR scientists have for the first time, identified that precise regulation of polyamine 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 , 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 editor:

See original here:
A*STAR scientists make groundbreaking discovery on stem cell regulation

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.

See the original post:
UCLA Scientists Identify Cell and Signaling Pathway that Regulates the Placental Blood Stem Cell Niche