Stem Cell Clinic

Researchers identify mechanism that maintains stem cells readiness

By Stem Cell Medical Center

An immune-system receptor plays an unexpected but crucially important role in keeping stem cells from differentiating and in helping blood cancer cells grow, researchers at UT Southwestern Medical Center report today in the journal Nature.

"Cancer cells grow rapidly in part because they fail to differentiate into mature cells. Drugs that induce differentiation can be used to treat cancers," said Dr. Chengcheng "Alec" Zhang, assistant professor in UT Southwestern's departments of physiology and developmental biology. "Our research identified a protein receptor on cancer cells that induces differentiation, and knowing the identity of this protein should facilitate the development of new drugs to treat cancers."

The family of proteins investigated in the study could help open a new field of biology integrating immunology with stem cell and cancer research, he added.

"The receptor we identified turned out to be a protein called a classical immune inhibitory receptor, which is known to maintain stemness of normal adult stem cells and to be important in the development of leukemia," he said.

Stemness refers to the blood stem cells' potential to develop into a range of different kinds of cells as needed, for instance to replenish red blood cells lost to bleeding or to produce more white blood cells to fight off infection. Once stem cells differentiate into adult cells, they cannot go back to being stem cells. Current thinking is that the body has a finite number of stem cells and it is best to avoid depleting them, Dr. Zhang explained.

Prior to this study, no high-affinity receptors had been identified for the family of seven proteins called the human angiopoetic-like proteins. These seven proteins are known to be involved in inflammation, supporting the activity of stem cells, breaking down fats in the blood, and growing new blood vessels to nourish tumors. Because the receptor to which these proteins bind had not been identified, the angiopoetic-like proteins were referred to as "orphans," he said.

The researchers found that the human immune-inhibitory receptor LILRB2 and a corresponding receptor on the surface of mouse cells bind to several of the angiopoetic-like proteins. Further studies, Dr. Zhang said, showed that two of the seven family members bind particularly well to the LILRB2 receptor and that binding exerts an inhibitory effect on the cell, similar to a car's brakes.

In the case of stem cells, inhibition keeps them in their stem state. They retain their potential to mature into all kinds of blood cells as needed but they don't use up their energy differentiating into mature cells. That inhibition helps stem cells maintain their potential to create new stem cells because in addition to differentiation, self-renewal is the cells' other major activity, Dr. Zhang said. He stressed that the inhibition doesn't cause them to create new stem cells but does preserve their potential to do so.

In future research, the scientists hope to find subtle differences between stem cells and leukemia cells that will identify treatments to block the receptors' action only in leukemia.

Journal reference: Nature

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Researchers identify mechanism that maintains stem cells readiness

UT Southwestern Researchers Identify Mechanism That Maintains Stem-Cell Readiness, Helps Leukemia Cells Growth

By Stem Cell Medical Center

Newswise DALLAS May 31, 2012 An immune-system receptor plays an unexpected but crucially important role in keeping stem cells from differentiating and in helping blood cancer cells grow, researchers at UT Southwestern Medical Center report today in the journal Nature.

Cancer cells grow rapidly in part because they fail to differentiate into mature cells. Drugs that induce differentiation can be used to treat cancers, said Dr. Chengcheng Alec Zhang, assistant professor in UT Southwesterns departments of physiology and developmental biology. Our research identified a protein receptor on cancer cells that inhibits differentiation, and knowing the identity of this protein should facilitate the development of new drugs to treat cancers.

The family of proteins investigated in the study could help open a new field of biology integrating immunology with stem cell and cancer research, he added.

The receptor we identified turned out to be a protein called a classical immune inhibitory receptor, which is known to maintain stemness of normal adult stem cells and to be important in the development of leukemia, he said.

Stemness refers to the blood stem cells potential to develop into a range of different kinds of cells as needed, for instance to replenish red blood cells lost to bleeding or to produce more white blood cells to fight off infection. Once stem cells differentiate into adult cells, they cannot go back to being stem cells. Current thinking is that the body has a finite number of stem cells and it is best to avoid depleting them, Dr. Zhang explained.

Prior to this study, no high-affinity receptors had been identified for the family of seven proteins called the human angiopoetic-like proteins. These seven proteins are known to be involved in inflammation, supporting the activity of stem cells, breaking down fats in the blood, and growing new blood vessels to nourish tumors. Because the receptor to which these proteins bind had not been identified, the angiopoetic-like proteins were referred to as orphans, he said.

The researchers found that the human immune-inhibitory receptor LILRB2 and a corresponding receptor on the surface of mouse cells bind to several of the angiopoetic-like proteins. Further studies, Dr. Zhang said, showed that two of the seven family members bind particularly well to the LILRB2 receptor and that binding exerts an inhibitory effect on the cell, similar to a cars brakes.

In the case of stem cells, inhibition keeps them in their stem state. They retain their potential to mature into all kinds of blood cells as needed but they dont use up their energy differentiating into mature cells. That inhibition helps stem cells maintain their potential to create new stem cells because in addition to differentiation, self-renewal is the cells other major activity, Dr. Zhang said. He stressed that the inhibition doesnt cause them to create new stem cells but does preserve their potential to do so.

In future research, the scientists hope to find subtle differences between stem cells and leukemia cells that will identify treatments to block the receptors action only in leukemia.

Other UT Southwestern researchers involved in the study from the departments of physiology and developmental biology include postdoctoral researchers Dr. ChangHao Cui, Dr. Xiaoli Chen, Dr. Chaozheng Zhang, Dr. HoangDinh Huynh, and Dr. Xunlei Kang; senior research associates Robert Silvany and Jiyuan Li; and graduate student Xuan Wan. Researchers from the department of immunology include former technician Alberto Puig Cant and Dr. E. Sally Ward, professor of immunology.

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UT Southwestern Researchers Identify Mechanism That Maintains Stem-Cell Readiness, Helps Leukemia Cells Growth

NeoStem to Present at Six Conferences in June

By Uncategorized

NEW YORK, May 31, 2012 (GLOBE NEWSWIRE) -- NeoStem, Inc. (NYSE Amex:NBS) ("NeoStem" or the "Company"), an international biopharmaceutical company focused on cell based therapies, announced today that Company management will present at six conferences in June.

International Society for Cellular Therapy Annual Meeting

National Investment Banking Association Conference

International Society for Stem Cell Research 10th Annual Meeting

The Biotechnology Industry Organization (BIO) International Conference

Alliance for Regenerative Medicine -- Clinical Outlooks for Regenerative Medicine 2012

Marcum's Inaugural MicroCap Conference

About NeoStem, Inc.

NeoStem, Inc. ("NeoStem") is a leader in the development and manufacture of cell therapies. NeoStem has a strategic combination of revenues, including that which is derived from the contract manufacturing services performed by Progenitor Cell Therapy, LLC, a NeoStem company. That manufacturing base is one of the few cGMP facilities available for contracting in the burgeoning cell therapy industry, and it is the combination of PCT's core expertise in manufacturing and NeoStem's extensive research capabilities that positions the company as a leader in cell therapy development. Amorcyte, LLC, also a NeoStem company, is developing a cell therapy for the treatment of cardiovascular disease. Amorcyte's lead compound, AMR-001, represents NeoStem's most clinically advanced therapeutic and is enrolling patients in a Phase 2 trial for the preservation of heart function after a heart attack. Amorcyte expects to begin a Phase 1 clinical trial in 2012/2013 for AMR-001 for the treatment of patients with congestive heart failure. Athelos Corporation, also a NeoStem company, is developing a T-cell therapy for a range of autoimmune conditions with its partner Becton-Dickinson. NeoStem's pre-clinical assets include its VSEL(TM) Technology platform for regenerative medicine, which NeoStem believes to be an endogenous, pluripotent, non-embryonic stem cell that has the potential to change the paradigm of cell therapy as we know it today.

For more information on NeoStem, please visit http://www.neostem.com.

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NeoStem to Present at Six Conferences in June

Malta opposing EU financing for stem cell research on embryos

By Uncategorized

Stem cell therapy may one day be used to cure disorders such as Fragile-X syndrome, or Cystic fibrosis and other genetic maladies.

Matthew Vella

The Maltese government wants the European Commission to abandon plans to provide funds for research activities on stem cells that involve "the destruction of human embryos".

In a declaration on the ethical principles for the Horizon 2020 programme, which is an 80 billion fund for the EU's programme for research and innovation to create new jobs, the Maltese government said it wanted more detailed guidelines on the bioethical principles that will guide research programmes.

Horizon 2020 will allow the financing of research on human stem cells - both adult and embryonic - as long as it is permitted by the national laws of member states.

The fund however will not finance human cloning, genetic modification, or the creation of human embryos intended for the purpose of research or stem cell procurement.

The European Commission does not explicitly solicit the use of human embryonic stem cells, but Horizon 2020 allows the use of human stem cells according to the objectives of the research, and only if it has the necessary approvals from the member states.

The Maltese declaration echoes previous statements by the Commission of Catholic Bishops of the EC (Comece), which said Horizon 2020 did not include greater protection of human embryos from stem cell research.

Malta says it does not want any such embryos to be used for stem cell research. The statement by the Maltese government said the Horizon 2020 programme "does not take sufficiently into account the therapeutic potential of human adult stem cells."

Malta wants Europe to commit to a reinforcement of research on human adult stem cells, and that Europe should abstain from financing matters of fundamental ethical principles, which differ among member states.

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Malta opposing EU financing for stem cell research on embryos

29 Johns Hopkins stem cell researchers awarded funding

By Stem Cell Treatment

Public release date: 30-May-2012 [ | E-mail | Share ]

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

This year the Maryland Stem Cell Research Fund awarded 29 of 40 grants to Johns Hopkins researchers for the study of stem cell metabolism and regulation, the creation of new cell models for human diseases such as schizophrenia and Rett syndrome, which previously could be studied only in animals, and the development of new potential therapies.

Researchers whose preliminary data promised greater discoveries were awarded Investigator-Initiated grants. Jeff Bulte, Ph.D., professor of radiology, biomedical engineering and chemical and biomolecular engineering and a member of the Institute for Cell Engineering, hopes to develop a cell therapy for treatment of type 1 diabetes an autoimmune disorder in which the immune system kills the insulin-producing cells that help regulate blood sugar. By developing cloaked stem and insulin-producing cells that can evade immune system detection, Bulte and his team hope to replace damaged cells and restore insulin levels in patients.

Grants were awarded to:

Several Johns Hopkins investigators were awarded Exploratory grants for researchers either new to the stem cell field or with untested but promising new ideas. Miroslaw Janowski , M.D., Ph.D., a research associate in radiology, plans to develop a stroke treatment by guiding newly introduced brain cells with magnets through blood vessels to the site of injury.

Exploratory grants were awarded to:

Postdoctoral trainees also will receive funding for research projects. A fellow in biomedical engineering, Pinar Huri, Ph.D., will use her award to develop bone grafts with blood vessels inside made from fat tissue-derived stem cells. The grafts would be used in patients with severely damaged bone in need of reconstructive surgery.

Postdoctoral grants were awarded to:

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29 Johns Hopkins stem cell researchers awarded funding

Breast stem-cell research: Receptor teamwork is required and a new pathway may be involved

By Stem Cell Medicine

Public release date: 30-May-2012 [ | E-mail | Share ]

Contact: Dian Land dj.land@hosp.wisc.edu 608-261-1034 University of Wisconsin-Madison

MADISON Breast-cancer researchers at the University of Wisconsin-Madison have found that two related receptors in a robust signaling pathway must work together as a team to maintain normal activity in mammary stem cells.

Mammary stem cells produce various kinds of breast cell types. They may also drive the development and growth of malignant breast tumors.

Published recently in the Journal of Biological Chemistry, the research also suggests that a new signaling pathway may be involved, a development that eventually could take cancer-drug manufacturers in a new direction.

"We wanted to know if we could use this knowledge to inform us about what might be the transition that occurs to start tumor growth and maintain it," says senior author Dr. Caroline Alexander, professor of oncology at the McArdle Laboratory for Cancer Research at the School of Medicine and Public Health.

The paper describes new information about the Wnt signaling pathway. Wnt signaling underlies numerous activities in normal development, but when the system is unregulated, cancer often occurs.

"Wnt signaling is very important for both stem cells and tumor growth. We need to know the details of the signaling process so that we can use the positive aspects of Wnt signaling for regenerative medicine, and eliminate the negative cancer-causing aspects," says Alexander, a member of the UW Carbone Cancer Center (CCC).

Regenerative biologists typically add Wnt proteins together with other agents to guide the differentiation of lung, bone and heart stem cells, she notes.

The UW researchers zeroed in on two related Wnt receptors on the cell surface--LRP5 and LRP6. The receptors normally respond to Wnt ligands that approach cells to initiate a signaling cascade inside.

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Breast stem-cell research: Receptor teamwork is required and a new pathway may be involved

Gaborone could have stem cell storage facility this year

By Stem Cell Treatment

Gaborone could have stem cell storage facility this year

LAWRENCE SERETSE Correspondent

Speaking to Mmegi this week, Mngqibisa said Parliament was set to pave the way for the facility by means of legislation in July and that Cryo-Save intended approaching government about storing stem cells for every Motswana.

"Stem cells are the basic building blocks of our bodies and are often referred to as 'master cells,'" she said.

"And because stem cells have the potential to become almost any other cell in the body, stem cell therapies are the way of the future."

Stem cell treatment is applied to over 70 diseases and disorders, among them leukemia, lymphoma, blood cancers and bone marrow disorders like aplastic anaemia and sickle cell disease.

Mngqibisa said patients requiring a haemopoietic stem transplant will receive cells from one or three sources of bone marrow, circulating blood or umbilical cord blood.

"It is much easier to match transplant patients with immune naive cord blood stem cells than with the other sources of stem cells," she explained. "Umbilical cord blood stem cells are the most naive stem cells, hence they are best harvested from the baby at birth before they are exposed to infections and immune reactions."

She said transplant patients recovered better when they received stem cells from a related donor rather than from an unrelated donor. Brain tumors, lung cancer, plasma cell leukemia, anaemia and osteopetrosis.

Multiple sclerosis and diabetes can also help in tissue building like skin burn repairs. The newborn may be able to use his or her cord blood for some of the conditions on a long list, but not all. In some cases, a matching sibling stem cell would be the first choice.

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Gaborone could have stem cell storage facility this year

LA BioMed's Dr. Patricia Dickson researching treatments for neurodegenerative disorders

By Stem Cell Medical Center

Public release date: 30-May-2012 [ | E-mail | Share ]

Contact: Diana Soltesz diana@dsmmedia.com 818-592-6747 Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed)

LOS ANGELES (May 30, 2012) Patricia Dickson, M.D., principal investigator at The Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed), is co-principal investigator of a project that was just awarded a $5.5 million grant from the California Institute for Regenerative Medicine (CIRM). The goal of the project is to develop a stem cell based therapy for the treatment of mucopolysaccharidosis I (MPS I), a fatal pediatric lysosomal storage disease that causes neurodegeneration as well as defects in other major organ systems. Dr. Dickson is working with lead investigator Philip H. Schwartz, Ph.D., senior scientist at the CHOC Children's Research Institute and managing director of the facility's National Human Neural Stem Cell Resource.

For nearly a decade, Dr. Dickson's research at LA BioMed has focused on enzyme replacement therapy for mucopolysaccharidosis, a group of metabolic disorders caused by the absence or malfunctioning of enzymes needed to break down molecules - called glycosaminoglycans - which help build bone, cartilage, connective tissue and other essential parts of the body. As part of this study, she and her colleagues will begin with proof-of-principle experiments for MPS I.

"Dr. Dickson has been at the forefront of mucopolysaccharidosis research for many years, working tirelessly to help develop therapies for MPS I," said David I. Meyer, Ph.D., president and CEO of LA BioMed. "We congratulate her on her continued success, and for her role in this project which could be an important breakthrough for children suffering from neurodegenerative disorders."

"The unique aspect of this research is that it uses a single donor for the transplantation of stem cells into the body and the brain, which allows the best treatment for both physical and neurological disease and avoids rejection of neural stem cell grafts by the host immune system," said Dr. Dickson. "Pediatric neurodegenerative diseases are generally neglected in stem cell research, but stand the greatest chance of success. The high probability of success, along with the need to alleviate suffering in children, is why we believe the first applications of stem cell therapies should be for these kids."

Dr. Schwartz, Dr. Dickson and project collaborators are working to address two critical issues in the development of a therapeutic candidate based on stem cells: that early intervention is not only required but is indeed possible in this patient population, and that the concept of immune tolerance is also required, where the immune system is trained to attack only real threats in the body but not the body's own cells or tissues.

To date, there is still a significant unmet medical need to better impact and prevent the neurodegenerative processes in this disease. If successful in MPS I, this technique can be expanded to help treat other neurodegenerative disorders due to lysosomal storage.

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