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VS-507 is a polyether natural product with a complex chemical structure that is currently being developed by Verastem as a Wnt inhibitor. Past research has shown that VS-507 inhibits Wnt signaling by blocking the phosphorylation of the Wnt coreceptors LPR5 and LRP6 and inducing their degradation. Under the terms of the research collaboration, Eisai will synthesize analogs of VS-507 by leveraging the natural product chemistry-based drug discovery platform it used to generate the anticancer agent Halaven(R) (eribulin mesylate) from the polyether macrolide natural product Halichondrin B. Verastem will utilize its proprietary Wnt signaling and cancer stem cell assays to evaluate the resulting analogs. Verastem will own any novel compounds generated, while Eisai earns a royalty on product sales and has a right of first negotiation to obtain commercialization rights. The identification of proteins involved in cancer has become possible due to advances being made in cancer genetics research. The integration of Eisai and Verastem's complementary platform technologies is expected to have significant synergistic effects in the development of novel compounds that regulate Wnt signaling.

Eisai defines oncology as an area of therapeutic focus and is committed to developing novel anticancer agents and treatments for supportive care. Through this research collaboration, Eisai seeks to make further contribution to address the diversified needs of, and increase the benefits provided to, cancer patients and their families as well as healthcare providers.

About Cancer Stem Cells

Cancer stem cells are cancer cells that possess characteristics associated with normal stem cells. Stem cells have two key features, namely self-renewal capacity (the ability to divide and give rise to new stem cells identical to the original stem cell) and multilineage differentiation potential (the ability to differentiate into various types of cells). Some researchers advocate the cancer stem cell theory, which puts forth the idea that cancer is caused by cancer stem cells that possess the same characteristics as stem cells. Cancer stem cells were first identified in acute myeloid leukemia in 1997, and have since been discovered in solid tumors and various other types of cancer.

About Wnt Signaling

Wnt is a glycoprotein with a molecular weight of approximately 40,000. It is stored in all types of living organisms from threadworms and drosophila to mammals, and has been reported to regulate the proliferation, differentiation and motility of cells during early development and axis formation, organogenesis, and after birth. Pathways known to comprise the Wnt signaling pathway include the Wnt/Beta-catenin pathway, which is associated with cell differentiation and dorsal formation, the Wnt/PCP pathway, which is involved in planar cell polarity and motility during gastrulation, the Wnt/Ca2+ pathway, which plays a role in embryonic isolation, and the pathway involved in the regulation of muscle regeneration. The Wnt/Beta-catenin pathway is the most well-known of all the Wnt signaling pathways. Beta-catenin acts as a Wnt signaling mediator to induce gene expression which results in the regulation of cell proliferation and differentiation.

About Verastem, Inc.

Headquartered in Massachusetts in the United States, Verastem, Inc. is a biopharmaceutical company focused on discovering and developing drugs to treat breast and other cancers by targeting cancer stem cells, an underlying cause of tumor recurrence and metastasis. For more information on Verastem, Inc., please visit http://www.verastem.com.

About Eisai

Eisai Co., Ltd. (TSE: 4523; ADR: ESALY) is a research-based human health care (hhc) company that discovers, develops and markets products throughout the world. Eisai focuses its efforts in three therapeutic areas: integrative neuroscience, including neurology and psychiatric medicines; integrative oncology, which encompasses oncotherapy and supportive-care treatments; and vascular/immunological reaction. 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 Co., Ltd., please visit http://www.eisai.com.

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Eisai Enters Research Collaboration with Verisam, Inc. for Small Molecule Wnt Inhibitors

THE discovery of a unique marker on stem cells from the gut, liver and pancreas could eventually allow scientists to diagnose cancer earlier and develop new treatments, a Melbourne scientist says.

Professor Martin Pera from Stem Cells Australia and an international team developed an antibody that identifies and isolates the marker, which sits on the outer surface of stem cells and another type of cell called a progenitor.

These cells are particularly hard to find in the pancreas and liver.

By identifying the markers, the cells can be isolated and extracted for study in the laboratory, where scientists can observe what happens to the cells during the disease process and in repair and regeneration.

Prof Pera, who is also chair of Stem Cell Sciences at the University of Melbourne, said the number of cells with the marker expanded during pancreatic and esophageal cancer, and liver cirrhosis.

"It may well be that they are precursors of the cancers," Prof Pera told AAP.

He said if the marker could be found in the blood of cancer patients, it could allow sufferers to be diagnosed earlier and provide new approaches to treatment, which could involve developing drugs to target the marker on cancer cells.

"Cancers of the liver, pancreas and oesophagus are often very difficult to detect and challenging to treat," Prof Pera said.

He will continue his investigations into liver, pancreatic and gut stem cells with Dr Kouichi Hasegawa, who conducts stem cell research in Japan and India.

The research was published in the journal Stem Cell.

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Stem cell discovery important for cancer

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.

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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.

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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.

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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.

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

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Finished heart switches stem cells off

Public release date: 11-Jul-2012 [ | E-mail | Share ]

Contact: David Eve celltransplantation@gmail.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (July 11, 2012) A research team in the Netherlands has found that cells from burn eschar, the non-viable tissue remaining after burn injury and normally removed to prevent infection, can be a source of mesenchymal cells that may be used for tissue engineering. Their study compared the efficacy of those cells to adipose (fat)-derived stem cells and dermal fibroblasts in conforming to multipotent mesenchymal stromal cell (MSC) criteria.

Their study is published in the current issue of Cell Transplantation (21:5), now freely available on-line at http://www.ingentaconnect.com/content/cog/ct/.

"In this study we used mouse models to investigate whether eschar-derived cells fulfill all the criteria for multipotent mesenchymal stromal cells as formulated by the International Society for Cellular Therapy (ISCT)," said study co-author Dr. Magda M.W. Ulrich of the Association of Dutch Burn Centres, The Netherlands. "The study also assessed the differentiation potential of MSCs isolated from normal skin tissue and adipose tissue and compared them to cells derived from burn eschar."

According to the researchers, advances in burn treatment have meant that the percentage of patients surviving severe burn injuries is increasing. This escalating survival rate has also increased the number of people who are left with burn scars, which lead to functional problems with the skin, such as contracture, and the social and psychological aspects of disfigurement.

Tissue engineering to rebuild the skin is the most promising approach to solving these problems. However, two problems arise with tissue engineering the source of the cells and the design of the scaffold aimed at creating a microenvironment to guide cells toward tissue regeneration.

"The choice of cells for skin tissue engineering is vital to the outcome of the healing process," said Dr. Ulrich. "This study used mouse models and eschar tissues excised between 11 and 26 days after burn injury. The delay allowed time for partial thickness burns to heal, a process that is a regular treatment option in the Netherlands and rest of Europe."

The researchers speculated that during this time the severely damaged tissues could attract stem cells from the surrounding tissues, as elevated levels of MSCs have been detected in the blood of burn victims.

"MSCs can only be beneficial to tissue regeneration if they differentiate into types locally required in the wound environment," noted Dr. Ulrich. "We concluded that eschar-derived MSCs represent a population of multipotent stem cells. The origin of the cells remains unclear, but their resemblance to adipose-derived stem cells could be cause for speculation that in deep burns the subcutaneous adipose tissue might be an important stem cell source for wound healing."

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Cells derived from debrided burn tissue may be useful for tissue engineering

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 an agreement with Pfizer for the exclusive in-license of worldwide commercial rights for VS-6063 (formerly PF-04554878), a focal adhesion kinase (FAK) inhibitor that has completed a Phase 1 clinical study in advanced solid tumors.

FAK is a non-receptor tyrosine kinase that regulates tumor cell proliferation and invasion. The targeted disruption of this pathway in preclinical models of cancer reduces cancer stem cells, primary tumor mass and metastasis.

Verastem has identified the FAK pathway as a critical regulator of the survival of cancer stem cells, which are an underlying cause of cancer recurrence and metastasis, said Robert Weinberg, Ph.D., Verastem co-founder and chair of the Scientific Advisory Board.

VS-6063 is being developed for the treatment of solid tumors. According to data presented at ASCO 2011 from a Phase 1 safety study of VS-6063 in 36 patients conducted by Pfizer, VS-6063 was well-tolerated and demonstrated signs of clinical activity to support further development. Verastem anticipates conducting clinical trials targeting solid tumor indications with VS-6063.

Like Pfizer, Verastem is committed to bringing innovative treatments to patients with cancer, said Garry Nicholson, President and General Manager of Pfizer Oncology. Verastems specific focus on targeting cancer stem cells makes them the ideal company to continue the development of this compound.

Under the terms of the agreement, Verastem will assume sole responsibility for global product development of VS-6063. Pfizer will receive an upfront payment in cash and Verastem equity, development milestones and royalties and milestones on future sales of VS-6063.

VS-6063 accelerates Verastems FAK inhibitor program with a clinical, Phase 2-ready product candidate targeting this key regulatory pathway for cancer stem cells, said Christoph Westphal, M.D., Ph.D., Chairman and Chief Executive Officer of Verastem. We believe our focus on identifying patients with a high cancer stem cell burden for treatment with our targeted therapies uniquely positions Verastem to lead the next wave of therapeutics in cancer.

Conference Call and Webcast Information Verastem will discuss the acquisition during the Research and Development Day to be held tomorrow, July 12, at 9:00am ET. A live webcast of the event can be accessed by visiting the investors section of the Companys website at http://www.verastem.com. A replay will be available for two weeks from the date of the event.

A live, listen-only conference call of the event can be accessed by dialing 1-866-700-7173 five minutes prior to the start of the event and providing the passcode 73322380.

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Verastem Acquires Clinical-Stage FAK Inhibitor from Pfizer

Johns Hopkins researchers have discovered that a single protein molecule may hold the key to turning cardiac stem cells into blood vessels or muscle tissue, according to a release from the university. This finding may lead to better ways to treat heart attack patients.

Human heart tissue typically forms scars rather than healing well after an attack. However, stem cells have been shown improve the repair process by turning into the cells that make up healthy heart tissue, including heart muscle and blood vessels. The recent discovery of a master molecule that guides the destiny of these stem cells has the potential to result in even more effective treatments for heart patients, the Johns Hopkins researchers say.

In a study published in the June 5 online edition of journal Science Signaling, the Johns Hopkins team reported that tinkering with a protein molecule called p190RhoGAP shaped the development of cardiac stem cells and prodded them to become the building blocks for either blood vessels or heart muscle. The scientists said that by altering levels of this protein, they were able to affect the future of these stem cells. In biology, finding a central regulator like this is like finding a pot of gold, said Andre Levchenko, a biomedical engineering professor and member of the Johns Hopkins Institute for Cell Engineering, who supervised the research effort.

The lead author of the journal article, Kshitiz, a postdoctoral fellow who uses only his first name, said, Our findings greatly enhance our understanding of stem cell biology and suggest innovative new ways to control the behavior of cardiac stem cells before and after they are transplanted into a patient. This discovery could significantly change the way stem cell therapy is administered in heart patients.

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"Master Molecule" May Help Heart Treatment

A virus infection Stephanie Connor acquired during pregnancy put her unborn daughter at significant risk for brain damage and lifelong hearing loss.

"It was traumatic," said Connor, of LaBelle, Fl, after learning about her daughter's condition. "It was like mourning the loss of a child."

At age 1, baby Madeleine was completely deaf in her right ear and her hearing was severely lost in the left, said Connor. While a hearing aid helped to amplify some sounds for Madeleine, it would never fully repair the damage in her ear.

But a simple experimental procedure that Connor enrolled in for Madeleine may have restored her hearing and reversed her condition.

In January 2012, Madeleine, 2, became the first child to undergo an experimental hearing loss treatment through an FDA-approved trial at Memorial Hermann-Texas Medical Center that infused stem cells from her own banked cord blood into her damaged inner ear.

Within the last six months, Connor says she's seen a dramatic improvement in Madeleine's ability to hear.

"Before, when she would hear something she would look all around," Connor said. "But now we notice that she turns in the right direction of the sound."

Madeleine was also able to speak for the first time, Connor said.

For more than two decades, umbilical cord blood transplantation -- either by a baby's own cord blood or another's, depending on the type of procedure -- has been used to treat otherwise fatal diseases including blood disorders, immune diseases, and some types of cancers.

Infusing cord blood stem cells into the body may also have the potential to heal and regenerate damaged cells and tissues.

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Cord Blood Stem Cells Restore Toddler's Hearing