Category Archives: Stem Cells

Public release date: 17-Jul-2012 [ | E-mail | Share ]

Contact: Vanessa McMains vmcmain1@jhmi.edu 410-502-9410 Johns Hopkins Medical Institutions

Johns Hopkins tissue engineers have used tiny, artificial fiber scaffolds thousands of times smaller than a human hair to help coax stem cells into developing into cartilage, the shock-absorbing lining of elbows and knees that often wears thin from injury or age. Reporting online June 4 in the Proceedings of the National Academy of Sciences, investigators produce an important component of cartilage in both laboratory and animal models. While the findings are still years away from use in people, the researchers say the results hold promise for devising new techniques to help the millions who endure joint pain.

"Joint pain affects the quality of life of millions of people. Rather than just patching the problem with short-term fixes, like surgical procedures such as microfracture, we're building a temporary template that mimics the cartilage cell's natural environment, and taking advantage of nature's signals to biologically repair cartilage damage," says Jennifer Elisseeff, Ph.D., Jules Stein Professor of Ophthalmology and director of the Translational Tissue Engineering Center at the Johns Hopkins University School of Medicine.

Unlike skin, cartilage can't repair itself when damaged. For the last decade, Elisseeff's team has been trying to better understand the development and growth of cartilage cells called chondrocytes, while also trying to build scaffolding that mimics the cartilage cell environment and generates new cartilage tissue. This environment is a 3-dimensional mix of protein fibers and gel that provides support to connective tissue throughout the body, as well as physical and biological cues for cells to grow and differentiate.

In the laboratory, the researchers created a nanofiber-based network using a process called electrospinning, which entails shooting a polymer stream onto a charged platform, and added chondroitin sulfatea compound commonly found in many joint supplementsto serve as a growth trigger. After characterizing the fibers, they made a number of different scaffolds from either spun polymer or spun polymer plus chondroitin. They then used goat bone marrow-derived stem cells (a widely used model) and seeded them in various scaffolds to see how stem cells responded to the material.

Elisseeff and her team watched the cells grow and found that compared to cells growing without scaffold, these cells developed into more voluminous, cartilage-like tissue. "The nanofibers provided a platform where a larger volume of tissue could be produced," says Elisseeff, adding that 3-dimensional nanofiber scaffolds were more useful than the more common nanofiber sheets for studying cartilage defects in humans.

The investigators then tested their system in an animal model. They implanted the nanofiber scaffolds into damaged cartilage in the knees of rats, and compared the results to damaged cartilage in knees left alone.

They found that the use of the nanofiber scaffolds improved tissue development and repair as measured by the production of collagen, a component of cartilage. The nanofiber scaffolds resulted in greater production of a more durable type of collagen, which is usually lacking in surgically repaired cartilage tissue. In rats, for example, they found that the limbs with damaged cartilage treated with nanofiber scaffolds generated a higher percentage of the more durable collagen (type 2) than those damaged areas that were left untreated.

"Whereas scaffolds are generally pretty good at regenerating cartilage protein components in cartilage repair, there is often a lot of scar tissue-related type 1 collagen produced, which isn't as strong," says Elisseeff. "We found that our system generated more type 2 collagen, which ensures that cartilage lasts longer."

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Nanoscale scaffolds and stem cells show promise in cartilage repair

Human neural stem cells. Courtesy UC Irvine radiation oncology professor Charles Limoli.

Human neural stem cells restored memory in mice with brain symptoms similar to Alzheimers disease, UC Irvine scientists reported Tuesday, opening the door to eventual treatment for human sufferers.

The announcement, made at an Alzheimers science conference in Vancouver, involves versatile though still largely mysterious neural stem cells grown in the lab by StemCells Inc., of Newark, Ca.

The cells, researchers at UCI and elsewhere have shown, can become many types of cells once injected into the body restoring limb movement in mice with crushed spines, halting blindness in rats and, now, improving memory and brain function in mice bred to exhibit the kinds of impairment seen in Alzheimers.

Youve probably heard about the God particle scientists have been working on, said Martin McGlynn, president and CEO of StemCells Inc. This isnt quite the God cell, but its an incredibly fascinating biological agent.

Over the past 12 to 18 months, scientists including Frank LaFerla, director of UCI MIND, worked on a treatment involving injection of the human neural stem cells into the brains of two kinds of mouse models those bred to model the effects of Alzheimers, and those bred to model the loss of neurons in a part of the brain known as the hippocampus.

Both animal models reported improvement in memory function, in a statistical way, McGlynn said.

Matthew Blurton-Jones, an assistant professor of neurobiology and behavior at UCI, presented the results of the Alzheimers work Tuesday at the Alzheimers Association International Conference.

Part of the scientists aim was to learn whether human neural cells placed in mice functioned as well as mouse neural cells.

That is one of the fascinating things about this, McGlynn said. They look like, smell like, walk like, dance like a human neural stem cell, (but) theyre fully regulated and submissive to the mouse, to the host.

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Stem-cell discovery: reversing Alzheimer's?

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Surgeon uses adult stem cell therapy in spinal fusion clinical trial

The Argonaut Interview: Dr. Hyun Bae

By Gary Walker

Stem cell research remains a controversial topic throughout much of the nation, for religious as well as ethical reasons. Embryonic stem cells, which can differentiate into extraembryonic tissues and are derived from human embryos, are a particularly hot-button topic.

Scientists and researchers around the globe have been exploring the potential that adult regenerative stem cells could have on patients suffering from a variety of ailments, including spinal cord injuries, heart conditions and diabetes.

While stem cell research - especially clinic studies involving human embryos - remains highly politicized, Californians have shown their support for the controversial therapy. Voters approved a 2004 initiative that allocated $3 million toward human embryonic stem cell research.

Proposition 71 made California the largest state-funded scientific research initiative in the United States.

Three years ago, President Barack Obama signed an executive order that reversed President George W. Bushs earlier policy of prohibiting the use of federal tax dollars for embryonic stem cell research.

Unlike embryonic cells, the use of adult stem cells in research and therapy is much less controversial. Dr. Hyun Bae, a spine surgeon at Saint Johns Health Center in Santa Monica, is the principal investigator in a clinical trial using adult stem cell technology. The hospital is one of only eight sites nationwide that have been chosen by the U.S. Food and Drug Administration for the studies.

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Surgeon uses adult stem cell therapy in spinal fusion clinical trial

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, hosted its annual Research and Development Day where Robert Weinberg, Ph.D., Verastem co-founder and chair of the Scientific Advisory Board, gave a seminar on cancer stem cells. Members of the Companys management team provided updates to the product portfolio and advancements in the research and development pipeline.

In order to generate a durable, clinical response in cancer we must design a treatment strategy that attacks the cancer stem cells, in addition to the other cancer cells, that comprise a tumor, said Dr. Weinberg. We founded Verastem in order to create therapies designed to specifically target cancer stem cells as these cells are resistant to standard cancer treatments. Verastem has made significant strides in the identification and development of small molecules that target this cancer stem cell population.

Yesterday, Verastem announced the acquisition of an exclusive license to VS-6063 (formerly PF-04554878) from Pfizer. VS-6063 is a focal adhesion kinase (FAK) inhibitor that has completed a Phase 1 clinical study in advanced solid tumors. VS-6063 was well tolerated and showed signs of clinical activity in the study.

A key component of Verastems IPO was to raise sufficient capital to rapidly progress the development of novel compounds targeting cancer stem cells, said Christoph Westphal, M.D., Ph.D., Verastem Chairman and Chief Executive Officer. With the in-license of VS-6063 from Pfizer, we have accelerated our clinical development plans for the FAK program by 12-18 months.

Our research has identified and prioritized key pathways necessary for the survival of cancer stem cells and yielded specific inhibitors to block these critical targets, said Jonathan Pachter, Ph.D., Verastem Vice President and Head of Research. We are now poised to translate that research into multiple clinical trials over the next year with our cancer stem cell-targeted agents.

Research and Development Day Program Highlights:

Focal Adhesion Kinase (FAK) Inhibition

FAK is amplified in human cancers and mediates survival of cancer stem cells in response to growth factors and integrin stimulation

Dual PI3K/mTOR Inhibition

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Verastem Discloses Research Results and Updated Clinical Plans at Research and Development Day

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)

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

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

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

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