Are women born with all the eggs they will ever have, or do they possess the ability to make more?

That debate is in full force this week as researchers led by Kui Liu at the University of Gothenburg in Sweden say they have ruled out the tantalising possibility that ovarian stem cells exist.

Back in February, Jonathan Tilly and his colleagues at Massachusetts General Hospital in Boston claimed that they had found stem cells in human ovaries. The news was incredible the cells were able to form new immature eggs, and it was hoped that they could be harnessed to improve in vitro fertilisation and help older women to conceive a healthy baby.

But it hasn't been easy to overturn the dogma that women are born with all the eggs that they will ever have.

The human ovary contains up to 2million immature eggs, and every month one of these matures and is released. It has been long-held that mammals are born with their lifetime's supply of eggs. That was until Tilly and various other groups discovered what they believed to be stem cells in mouse ovaries. The groups said that these cells were able to divide into new egg cells.

As these ovarian stem cells mature, a protein called vasa gets pulled from the surface of the cell into the centre, says Tilly. So his team looked for cells with vasa still on their surface in human ovarian tissue. They found a small number and identified them as stem cells because when they were removed from the tissue and placed inside a mouse, they divided into new cells capable of forming early-stage eggs.

Liu's team used a different approach. They used a mouse genetically modified to make all its cells glow green. They bred this mouse with another transgenic mouse that carries a piece of DNA that recognises vasa and changes the colour of only those cells that carry it. As a result, all of their offsprings' cells are green except those containing vasa, which appear red, yellow or blue.

The group monitored the cells that weren't green for three days. "These cells never proliferate," says Liu. What's more, when his team injected the non-green cells into a piece of mouse ovary, they were not able to make eggs.

"We've found that these cells are not really stem cells," says Liu. While the cells might look like stem cells, they don't act in the same way, he says. "We're not sure what they are."

Tilly stands by his discovery. He points out that it is difficult for Liu's team to rule out his findings because they did not use the same technique.

Visit link:
Debate over existence of ovarian stem cells heats up

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

Verastem, Inc., (VSTM) a biopharmaceutical company focused on discovering and developing drugs to treat breast and other cancers by targeting cancer stem cells, announced a research collaboration with Eisai for the next-generation of small molecule Wnt inhibitors.

Verastem scientific co-founder and chair of the Scientific Advisory Board, Robert Weinberg, Ph.D., published a report in 2011 in the journal Cell describing the critical nature of the Wnt pathway in the development and maintenance of cancer stem cells.

Verastem and Eisai have a shared vision for the utility of Wnt inhibitors in the treatment of cancer, said Jonathan Pachter, Ph.D., Verastem Vice President and Head of Research. Our Wnt inhibitor, VS-507, shows activity in multiple cancer stem cell models both in vitro and in human tumor xenografts. Through this collaboration with Eisai, a world leader in complex natural product chemistry, we can jointly leverage our unique capabilities to develop the next-generation of Wnt inhibitors for the targeted killing of cancer stem cells.

VS-507 is a proprietary formulation of salinomycin and will be the starting point for the development of proprietary analogs in the collaboration with Eisai. The resulting compounds will be tested in Verastems Wnt signaling and cancer stem cell assays to evaluate their selective activity. Verastem will own the analogs that are generated in the 12-month collaboration. Eisai will be eligible to receive royalties on commercial sales of identified products. During the term of the agreement, Eisai has a right of first negotiation for products that are created through the collaboration.

With their particular expertise in natural product chemistry, Eisai is the perfect partner, said Robert Forrester, Verastem Chief Operating Officer. We believe Wnt signaling is a critical regulator of cancer stem cells, and a combined research effort to find novel inhibitors of this pathway is of great interest to both Eisai and Verastem.

About Verastem, Inc.

Verastem, Inc. (VSTM) is a biopharmaceutical company focused on discovering and developing drugs to treat breast and other cancers by targeting cancer stem cells. Cancer stem cells are an underlying cause of tumor recurrence and metastasis. For more information please visit http://www.verastem.com.

About Eisai Co., Ltd.

Eisai Co., Ltd. is a research-based human health care (hhc) company that discovers, develops and markets products throughout the world. Through a global network of research facilities, manufacturing sites and marketing subsidiaries, Eisai actively participates in all aspects of the worldwide healthcare system. For more information about Eisai, please visit http://www.eisai.com.

More:
Verastem Enters Research Collaboration with Eisai for Small Molecule Wnt Inhibitors

REDWOOD CITY, Calif.--(BUSINESS WIRE)--

OncoMed Pharmaceuticals, Inc., a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, today announced that patient dosing has begun in a Phase I clinical trial of OMP-54F28 in patients with advanced solid tumor cancers. OMP-54F28 is OncoMeds fourth drug to enter clinical development. OMP-54F28 is a proprietary fusion protein based on a truncated form of the Frizzled8 receptor, or Fzd8, and is the companys second Wnt pathway modulator to enter the clinic as part of the collaboration between OncoMed and Bayer HealthCare Pharmaceuticals. OncoMeds first Wnt pathway targeting drug in the clinic is OMP-18R5, a monoclonal antibody targeting the Frizzled receptors. OMP-18R5 continues to advance in the clinic.

The Phase I clinical trial of OMP-54F28 is an open-label dose escalation study in patients with advanced solid tumors for which there is no remaining standard curative therapy. These patients are assessed for safety, immunogenicity, pharmacokinetics, biomarkers, and initial signals of efficacy.

The trial is being conducted at Pinnacle Oncology Hematology in Scottsdale, Arizona, the University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, and the University of Colorado Cancer Center under the direction of Principal Investigators Dr. Michael S. Gordon, Dr. David Smith and Dr. Antonio Jimeno, respectively. According to Dr. Gordon, who treated the first patient with OMP-54F28, It is exciting to bring novel agents such as OMP-54F28 that target key cancer pathways such as Wnt into the clinic. We believe that this investigational therapy has great potential based on its preclinical evidence of anti-tumor activity.

OncoMed believes that OMP-54F28 is a potent antagonist of the Wnt pathway, a key cancer stem cell pathway. OMP-54F28 has shown evidence of anti-tumor activity and reduction of CSC frequency in multiple preclinical models either as a single agent or when combined with chemotherapy. OncoMed has worked collaboratively with Bayers US affiliate Bayer HealthCare, LLC to manufacture the clinical supply of OMP-54F28 for this program. Bayer Pharma AG retains an option to exclusively license OMP-54F28 at any point through completion of certain Phase I trials.

The advancement of a second clinical molecule targeting the Wnt pathway is an important milestone for us and our collaboration with Bayer, said Paul Hastings, President and Chief Executive Officer of OncoMed Pharmaceuticals. In less than two years, we have successfully created a strong body of preclinical data for two distinct approaches and thereby expanded our clinical pipeline of potential first-in-class anti-cancer stem cell therapeutics.

About Cancer Stem Cells

Cancer stem cells, or CSCs, are the subpopulation of cells in a tumor responsible for driving growth and metastasis of the tumor. CSCs, also known as tumor-initiating cells, exhibit certain properties which include the capacity to divide and give rise to new CSCs via a process called self-renewal and the capacity to differentiate or change into the other cells that form the bulk of the tumor. Common cancer drugs target bulk tumor cells but have limited impact on CSCs, thereby providing a path for recurrence of the tumor. OncoMeds product candidates target CSCs by blocking self-renewal and driving differentiation of CSCs toward a non-tumorigenic state, and also impact bulk tumor cells. We believe OncoMeds product candidates are distinct from the current generations of chemotherapies and targeted therapies, and have the potential to significantly impact cancer treatment and the clinical outcome of patients with cancer.

About the Wnt Pathway

The Wnt pathway is an evolutionarily conserved signaling pathway that mediates cellular communication and regulates stem cell fate. Wnt signals through Frizzled receptors to stabilize beta-catenin and subsequently regulate gene expression. Fzd8-Fc acts as a decoy receptor and functions by sequestering Wnts so that they are unable to bind to Frizzled receptors. The Wnt pathway has been intensively studied and is now known to be inappropriately activated in many major tumor types, including colon, breast, liver, lung and pancreatic cancers, and is critical for the function of CSCs. Because of this extensive validation, the Wnt pathway has been a major focus of anti-cancer drug discovery efforts. OncoMed believes that Fzd8-Fc (OMP-54F28) and anti-Fzd7 (OMP-18R5) are two of the first therapeutic agents targeting this key pathway to enter clinical testing.

See the article here:
OncoMed Pharmaceuticals Initiates Phase I Clinical Trial of Anti-Cancer Stem Cell Therapeutic OMP-54F28 (Fzd8-Fc)

ScienceDaily (July 12, 2012) Transcription factor Ajuba regulates stem cell activity in the heart during embryonic development. It is not unusual for babies to be born with congenital heart defects. This is because the development of the heart in the embryo is a process which is not only extremely complex, but also error-prone. Scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim have now identified a key molecule that plays a central role in regulating the function of stem cells in the heart. As a result, not only could congenital heart defects be avoided in future, but new ways of stimulating the regeneration of damaged hearts in adults may be opened up.

It's a long road from a cluster of cells to a finished heart. Cell division transforms what starts out as a collection of only a few cardiac stem cells into an ever-larger structure from which the various parts of the heart, such as ventricles, atria, valves and coronary vessels, develop. This involves the stem and precursor cells undergoing a complex process which, in addition to tightly regulated cell division, also includes cell migration, differentiation and specialisation. Once the heart is complete, the stem cells are finally switched off.

Scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim have now discovered how major parts of this development process are regulated. Their search initially focused on finding binding partners for transcription factor Isl1. Isl1 is characteristic of a specific group of cardiac stem cells which are consequently also known as Isl1+ cells. During their search, the researchers came across Ajuba, a transcription factor from the group of LIM proteins. "We then took a closer a look at the interaction between these two molecules and came to the conclusion that Ajuba must be an important switch," says Gergana Dobreva, head of the "Origin of Cardiac Cell Lineages" Research Group at the Bad Nauheim-based Max Planck Institute.

Using an animal model, the scientists then investigated the effects of a defective switch on cardiac development. Embryonic development can be investigated particularly effectively in the zebrafish. The Bad Nauheim-based researchers therefore produced a genetically modified fish that lacked a functioning Ajuba protein. Cardiac development in these fishes was in fact severely disrupted. In addition to deformation of the heart, caused by twisting of the cardiac axis, what particularly struck the researchers was a difference in size in comparison with control animals. "In almost all the investigated fish we observed a dramatic enlargement of the heart. If Ajuba is absent, there is clearly no other switch that finally silences the Isl1-controlled part of cardiac development," says Dobreva.

Further investigations revealed that the enlargement of the heart is in fact attributable to a greatly increased number of cardiac muscle cells. The reason for this was in turn that the number of Isl1+ cells, i.e. the cardiac muscle precursor cells, was distinctly raised right from an early phase of development. Ajuba is a decisive factor in controlling stem cell activity: it binds to Isl1 molecules, thus blocking their stimulant effect.

The results from the study could have potential future applications. "Once we understand how cardiac development is regulated, we will also be more familiar with the causes of congenital heart defects and will consequently be able to consider therapeutic approaches," comments Dobreva. Damaged adult hearts can also be repaired in this way: "One possibility would be to optimise the production of replacement cells from embryonic or artificially produced stem cells in the laboratory. Silencing Ajuba in these cells might enhance their development into functional cardiac muscle cells. Sufficient replacement cells for treating patients could be cultured in this way." Another possibility is to stimulate stem cell activity by silencing Ajuba in the damaged heart and so cause the heart to regenerate itself. Further studies are now set to investigate how feasible this might be.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by Max-Planck-Gesellschaft.

View original post here:
Finished heart switches stem cells off