Category Archives: Stem Cell Research

Editor's Choice Main Category: Ear, Nose and Throat Also Included In: Radiology / Nuclear Medicine;Cancer / Oncology;Stem Cell Research Article Date: 11 May 2012 - 10:00 PDT

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The researchers note this finding could enhance the quality of life of 500,000 individuals with head and neck cancer each year worldwide.

The team found that the stem cells needed for regenerating the parotid gland (the largest pair of salivary glands) were primarily located in the major ducts of the gland. According to the researchers, these cells could be easily avoided during radiotherapy or given a minimal radiation dose.

Dr. Peter van Luijk, a research associate at the University Medical Center Groningen, The Netherlands, explained:

Findings from the study were presented at the 31st conference of the European Society for Radiotherapy and Oncology (ESTRO31).

Dry mouth syndrome is a condition in which there is not enough saliva in the mouth. The condition can occur when the parotid gland stops functioning properly after radiation damage.

Symptoms of dry mouth syndrome include difficulty sleeping, eating, tooth decay or loss, and bad breath. These symptoms lead to poorer quality of life and difficulty working, as well as social isolation.

The majority of treatments to treat the condition and its consequences are insufficient and can cost hundreds or even thousands of Euros per patient each year.

Dr. van Luijk said:

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Using Stem Cell Therapy For Neck And Head Cancers Avoids Salivary Gland Damage Caused By Radiotherapy

Newswise New research findings show that embryonic stem cells unable to fully compact the DNA inside them cannot complete their primary task: differentiation into specific cell types that give rise to the various types of tissues and structures in the body.

Researchers from the Georgia Institute of Technology and Emory University found that chromatin compaction is required for proper embryonic stem cell differentiation to occur. Chromatin, which is composed of histone proteins and DNA, packages DNA into a smaller volume so that it fits inside a cell.

A study published on May 10, 2012 in the journal PLoS Genetics found that embryonic stem cells lacking several histone H1 subtypes and exhibiting reduced chromatin compaction suffered from impaired differentiation under multiple scenarios and demonstrated inefficiency in silencing genes that must be suppressed to induce differentiation.

While researchers have observed that embryonic stem cells exhibit a relaxed, open chromatin structure and differentiated cells exhibit a compact chromatin structure, our study is the first to show that this compaction is not a mere consequence of the differentiation process but is instead a necessity for differentiation to proceed normally, said Yuhong Fan, an assistant professor in the Georgia Tech School of Biology.

Fan and Todd McDevitt, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, led the study with assistance from Georgia Tech graduate students Yunzhe Zhang and Kaixiang Cao, research technician Marissa Cooke, and postdoctoral fellow Shiraj Panjwani.

The work was supported by the National Institutes of Healths National Institute of General Medical Sciences (NIGMS), the National Science Foundation, a Georgia Cancer Coalition Distinguished Scholar Award, and a Johnson & Johnson/Georgia Tech Healthcare Innovation Award.

To investigate the impact of linker histones and chromatin folding on stem cell differentiation, the researchers used embryonic stem cells that lacked three subtypes of linker histone H1 -- H1c, H1d and H1e -- which is the structural protein that facilitates the folding of chromatin into a higher-order structure. They found that the expression levels of these H1 subtypes increased during embryonic stem cell differentiation, and embryonic stem cells lacking these H1s resisted spontaneous differentiation for a prolonged time, showed impairment during embryoid body differentiation and were unsuccessful in forming a high-quality network of neural cells.

This study has uncovered a new, regulatory function for histone H1, a protein known mostly for its role as a structural component of chromosomes, said Anthony Carter, who oversees epigenetics grants at NIGMS. By showing that H1 plays a part in controlling genes that direct embryonic stem cell differentiation, the study expands our understanding of H1s function and offers valuable new insights into the cellular processes that induce stem cells to change into specific cell types.

During spontaneous differentiation, the majority of the H1 triple-knockout embryonic stem cells studied by the researchers retained a tightly packed colony structure typical of undifferentiated cells and expressed high levels of Oct4 for a prolonged time. Oct4 is a pluripotency gene that maintains an embryonic stem cells ability to self-renew and must be suppressed to induce differentiation.

H1 depletion impaired the suppression of the Oct4 and Nanog pluripotency genes, suggesting a novel mechanistic link by which H1 and chromatin compaction may mediate pluripotent stem cell differentiation by contributing to the epigenetic silencing of pluripotency genes, explained Fan. While a significant reduction in H1 levels does not interfere with embryonic stem cell self-renewal, it appears to impair differentiation.

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Successful Stem Cell Differentiation Requires DNA Compaction

Philippine Daily Inquirer

Former President and current Pampanga Rep. Gloria Macapagal-Arroyo, who was suffering from a mineral deficiency in her bones arising from two corrective surgeries last September, wanted to seek alternative stem cell therapy abroad.

However, she was barred from leaving the country last November after Justice Secretary Leila de Lima refused to honor the temporary restraining order issued by the high court on the inclusion of Arroyo and her husband Jose Miguel Mike Arroyo in the immigration bureaus watch list.

In the wake of Arroyos supposed plan to try the radical technology at stem cell centers abroad to cure what her doctors here described as a rare bone disease, a province mate and a colleague of the former President filed a bill to put up a stem cell center in the country.

Pampanga Rep. Carmelo F. Lazatin, a member of the minority bloc in Congress, has filed House Bill No. 5287 mandating the establishment of a research facility to explore the benefits of stem cell technology as a potential cure for incurable diseases.

Blank cells

Stem cells, the foundation of every organ, tissue and cell within the human body, are like blank cells that do not yet have a specific physiological function, according to Harvard Stem Cell Institute (HSCI).

But when proper conditions in the body or in the laboratory occur, stem cells develop into specialized tissues and organs, HSCI explains in its website, adding that there are two sources of stem cells used in research: the adult stem cells and embryonic stem cells.

Adult stem cells are found in differentiated tissues and organs throughout the body while embryonic stem cells are obtained from the inner cell mass of a blastocyst, the ball of cells formed when the fertilized egg or zygote divides and forms two cells, then again to form four and so on, HSCI said.

In 2008, the Vatican issued a sweeping document on bioethical issues titled Dignitas Personae or The Dignity of the Person, taking into account recent developments in biomedical technology and reinforcing the Churchs opposition to embryonic stem cell research, in vitro fertilization, human cloning and genetic testing on embryos before implantation.

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In The Know: Stem cell therapy

ScienceDaily (May 11, 2012) New research findings show that embryonic stem cells unable to fully compact the DNA inside them cannot complete their primary task: differentiation into specific cell types that give rise to the various types of tissues and structures in the body.

Researchers from the Georgia Institute of Technology and Emory University found that chromatin compaction is required for proper embryonic stem cell differentiation to occur. Chromatin, which is composed of histone proteins and DNA, packages DNA into a smaller volume so that it fits inside a cell.

A study published on May 10, 2012 in the journal PLoS Genetics found that embryonic stem cells lacking several histone H1 subtypes and exhibiting reduced chromatin compaction suffered from impaired differentiation under multiple scenarios and demonstrated inefficiency in silencing genes that must be suppressed to induce differentiation.

"While researchers have observed that embryonic stem cells exhibit a relaxed, open chromatin structure and differentiated cells exhibit a compact chromatin structure, our study is the first to show that this compaction is not a mere consequence of the differentiation process but is instead a necessity for differentiation to proceed normally," said Yuhong Fan, an assistant professor in the Georgia Tech School of Biology.

Fan and Todd McDevitt, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, led the study with assistance from Georgia Tech graduate students Yunzhe Zhang and Kaixiang Cao, research technician Marissa Cooke, and postdoctoral fellow Shiraj Panjwani.

The work was supported by the National Institutes of Health's National Institute of General Medical Sciences (NIGMS), the National Science Foundation, a Georgia Cancer Coalition Distinguished Scholar Award, and a Johnson & Johnson/Georgia Tech Healthcare Innovation Award.

To investigate the impact of linker histones and chromatin folding on stem cell differentiation, the researchers used embryonic stem cells that lacked three subtypes of linker histone H1 -- H1c, H1d and H1e -- which is the structural protein that facilitates the folding of chromatin into a higher-order structure. They found that the expression levels of these H1 subtypes increased during embryonic stem cell differentiation, and embryonic stem cells lacking these H1s resisted spontaneous differentiation for a prolonged time, showed impairment during embryoid body differentiation and were unsuccessful in forming a high-quality network of neural cells.

"This study has uncovered a new, regulatory function for histone H1, a protein known mostly for its role as a structural component of chromosomes," said Anthony Carter, who oversees epigenetics grants at NIGMS. "By showing that H1 plays a part in controlling genes that direct embryonic stem cell differentiation, the study expands our understanding of H1's function and offers valuable new insights into the cellular processes that induce stem cells to change into specific cell types."

During spontaneous differentiation, the majority of the H1 triple-knockout embryonic stem cells studied by the researchers retained a tightly packed colony structure typical of undifferentiated cells and expressed high levels of Oct4 for a prolonged time. Oct4 is a pluripotency gene that maintains an embryonic stem cell's ability to self-renew and must be suppressed to induce differentiation.

"H1 depletion impaired the suppression of the Oct4 and Nanog pluripotency genes, suggesting a novel mechanistic link by which H1 and chromatin compaction may mediate pluripotent stem cell differentiation by contributing to the epigenetic silencing of pluripotency genes," explained Fan. "While a significant reduction in H1 levels does not interfere with embryonic stem cell self-renewal, it appears to impair differentiation."

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Successful stem cell differentiation requires DNA compaction, study finds

Connie K. Ho for RedOrbit.com

A new study by researchers at the University of California, Los Angeles (UCLA) has discovered two adult stem cell-like subpopulations in adult human skin.

The findings allow for further research to be done in the area of personalized medicine and patient-specific cellular therapies.

The study, using technology from Fibrocell Science, allowed the researchers to identify and confirm two types of cells in human skin cell cultures; the possible source of stem cell-like subpopulations from skin biopsies would be faster to perform, painless, and less invasive than current extractions from adipose tissues and bone marrow.

The research, featured in the inaugural issue of BioResearch Open Access, discusses two subtypes of cells. BioResearch Open Access is a bimonthly, peer-reviewed journal. It features scientific topics like biochemistry, bioengineering, gene therapy, genetics, microbiology, neuroscience, regenerative medicine, stem cells, systems biology, tissue engineering and biomaterials, and virology.

Being able to identify two sub-populations of rare, viable and functional cells that behave like stem cells from within the skin is an important finding because both cell types have the potential to be investigated for diverse clinical applications, commented Dr. James A. Bryne, lead author of the report.

Brynes research, first at Stanford University then at UCLA, focused on reprogramming beginnings of cells from animals and then humans. A graduate of Cambridge University, Bryne studied the intra- and inter-species of epigenetic reprogramming. His work also highlighted how primate embryonic stem cells could be derived from somatic cell nuclear transfers.

The study published in BioResearch Open Access confirmed previous research that identified a rare population of cells in adult human skin that had a marker called stage-specific embryonic antigen 3 (SSEA3). Bryne and his colleagues found that there was an increase in the amount of SSEA3 expressing cells after injury to the human skin. It showed that the SSEA3 biomarker could be used to help identify and isolate cells with tissue-regenerative traits.

Finding these rare adult stem cell-like subpopulations in human skin is an exciting discovery and provides the first step towards purifying and expanding these cells to clinically relevant numbers for application to a variety of potential personalized cellular therapies for osteoarthritis, bone loss, injury and/or damage to human skin as well as many other diseases, remarked Bryne, an Assistant Professor of Molecular and Medical Pharmacology at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Bryne and his team used Fibrocell technology to collect cells from skin samples, cultured the cells in the lab, and purified them by fluorescence-activated cell sorting (FACS). The FACS tagged suspended cells with fluorescent markers for undifferentiated stem cells. The researchers were able to separate the rare cell subpopulations from other kinds of cells.

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Study Identifies Cell Subtypes For Potential Personalized Cellular Therapies

NEWARK, Calif., May 10, 2012 (GLOBE NEWSWIRE) -- StemCells, Inc. (Nasdaq:STEM - News), a leading stem cell company developing and commercializing novel cell-based therapeutics and tools for use in stem cell-based research and drug discovery, today reported financial results for the first quarter ended March 31, 2012 and provided a business update.

"The first quarter of 2012 turned out to be pivotal in the Company's pursuit of cell-based therapeutics for a broad array of CNS disorders," said Martin McGlynn, President and CEO of StemCells, Inc. "Data from our Phase I trial completed in February, which was designed to evaluate the safety and preliminary efficacy of our proprietary HuCNS-SC(R) neural stem cells in a rare myelination disorder, provided us with the clinical breakthrough that we had been seeking. We have now established proof of principle that our cells are capable of myelinating nerve axons in an appropriate, progressive and durable way in the brains of patients with a severe myelination disorder. Moreover, we observed measurable gains in motor and/or cognitive function in three of the four patients, while the fourth remained clinically stable. We believe this is a departure from the natural history of this fatal disease. This is great news for the PMD community and in due course we will meet with the FDA to discuss the conduct of a controlled Phase II study. The results of the study should also provide encouragement to the large community of patients, caregivers and clinicians dealing with more common myelination disorders, such as multiple sclerosis and cerebral palsy. We plan to meet with experts to help us develop a strategy to quickly and efficiently evaluate our cells in these more common myelination disorders."

"It remains our belief," continued Mr. McGlynn, "that the best pathway for growing shareholder value is for the Company to continue generating meaningful clinical data for our HuCNS-SC program in a thoughtful, cost effective manner. As our financial results show, we are carefully controlling our expenses and our cash burn. And as our PMD trial data shows, meaningful data from our extensive and expanding clinical development program has begun to emerge."

First Quarter and Recent Business Highlights

Therapeutic Product Development

Tools and Technologies Programs

Other Business Activities

First Quarter Financial Results

Revenue from product sales in the first quarter of 2012 was $271,000, an 82% increase over the first quarter of 2011. This growth was driven by increased unit volumes in our SC Proven media and reagents business. Revenue from licensing agreements and grants in the first quarter of 2012 was $373,000, due mainly to receipt of fees from a license agreement with genOway.

Research and development expenses were 29% lower in the first quarter of 2012 compared to the same period in 2011, while selling, general and administrative expenses declined by 7%. The significant reduction in operating expenses was primarily attributable to the reduction in workforce effected in May 2011, relocation of our corporate headquarters in July 2011 and other cost containment measures.

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StemCells, Inc. Reports First Quarter 2012 Financial Results and Provides Business Update

A stem cell breakthrough at UCLA could mark a big step for a biopharmaceutical company to use its proprietary technology to forge partnerships with pharmaceutical companies and other research institutions.

Fibrocell Sciences technology isolates, purifies and multiplies a patients fibroblast cells, connective skin cells that make collagen. In a research collaboration with the company, UCLA used the technology to isolate, identify and increase the number of different skin cell types, which lead to two rare adult stem cell-like subpopulations being identified in adult human skin SSEA3-expressing regeneration-associated cells associated with skin regeneration after injuries and mesenchymal adult stem cells.

The findings could have broad applications for personalized medicine. Currently, adult stem cells are derived from adipose tissue and bone marrow. Using mesenchymal stem cells would be less invasive and could be more efficient. Mesenchymal stem cells are being used in research to develop osteoblasts, or bone cells; chondrocytes, or cartilage cells; and adipocytes, or fat cells.

David Pernock, the chairman and CEO of Fibrocell, said the move could mark a significant step in the companys growth.

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Stem cell collaboration could set stage for company’s growth

CARLSBAD, Calif.--(BUSINESS WIRE)--

International Stem Cell Corporation (OTCBB: ISCO.OB - News) http://www.internationalstemcell.com today announced that the Company has developed new technologies to commercialize the use of human parthenogenetic stem cells (hpSC) to treat human diseases. The methods announced today are capable of producing populations of stem cells and their therapeutically valuable derivatives not only to a higher level of purity but also at a cost that is approximately several times lower than previously reported techniques.

ISCOs research team has developed a new method to derive high-purity populations of neural stem cells (NSC) from hpSC and further differentiate them into dopaminergic neurons. This method is capable of generating sufficient quantities of neuronal cells for ISCOs pre-clinical and clinical studies and is highly efficient as it requires substantially less time and labor in addition to using fewer costly materials than traditional methods. ISCOs technologies make possible the creation of billions of neuronal cells necessary for conducting such studies from a small batch of stem cells.

ISCO has also announced today that it has developed a new high-throughput cell culture method for growing human parthenogenetic stem cells (hpSC) in large quantities. This new technique is easily scalable and can produce the quantities of cGMP grade hpSC necessary for commercial and therapeutic applications.

One of the most challenging issues in commercializing stem cell based treatments is creating high-purity populations of stem cell derivatives at a reasonable cost. I believe the new methods we have developed solve this important problem and help position us for future clinical studies, says Dr. Ruslan Semechkin, Vice President, R&D.

About International Stem Cell Corporation

International Stem Cell Corporation is focused on the therapeutic applications of human parthenogenetic stem cells (hpSCs) and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in the creation of pluripotent human stem cells from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells for hundreds of millions of individuals of differing genders, ages and racial background with minimal immune rejection after transplantation. hpSCs offer the potential to create the first true stem cell bank, UniStemCell. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology, and stem cell-based skin care products through its subsidiary Lifeline Skin Care (www.lifelineskincare.com). More information is available at http://www.internationalstemcell.com or follow us on Twitter @intlstemcell.

To receive ongoing corporate communications, please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

Forward-looking Statements

Statements pertaining to anticipated developments, the potential benefits of research programs and new manufacturing technologies, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products and technologies regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update forward-looking statements.

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International Stem Cell Corporation Announces New Stem Cell Manufacturing Technologies to Support its Therapeutic ...

ScienceDaily (May 4, 2012) Fibroid uterine tumors affect an estimated 15 million women in the United States, causing irregular bleeding, anemia, pain and infertility. Despite the high prevalence of the tumors, which occur in 60 percent of women by age 45, the molecular cause has been unknown.

New Northwestern Medicine preclinical research has for the first time identified the molecular trigger of the tumor -- a single stem cell that develops a mutation, starts to grow uncontrollably and activates other cells to join its frenzied expansion.

"It loses its way and goes wild," said Serdar Bulun, M.D., the chair of obstetrics and gynecology at Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital. "No one knew how these came about before. The stem cells make up only 1 percent of the cells in the tumor, yet they are the essential drivers of its growth."

The paper is published in the journal PLoS ONE. Masanori Ono, M.D., a post-doctoral student in Bulun's lab, is the lead author.

The stem cell initiating the tumor carries a mutation called MED12. Recently, mutations in the MED12 gene have been reported in the majority of uterine fibroid tissues. Once the mutation kicks off the abnormal expansion, the tumors grow in response to steroid hormones, particularly progesterone.

For the study, researchers examined the behavior of human fibroid stem cells when grafted into a mouse, a novel model initiated by Northwestern scientist Takeshi Kurita, a research associate professor of obstetrics and gynecology. The most important characteristic of fibroid stem cells is their ability to generate tumors. Tumors originating from the fibroid stem cell population grew 10 times larger compared to tumors initiated with the main cell population, suggesting a key role of these tumor stem cells is to initiate and sustain tumor growth.

"Understanding how this mutation directs the tumor growth gives us a new direction to develop therapies," said Bulun, also the George H. Gardner Professor of Clinical Gynecology.

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A single stem cell mutation triggers fibroid tumors: Mutated stem cell 'goes wild' in frenzied tumor expansion

(SACRAMENTO, Calif.) -- UC Davis Health System researchers are a step closer to launching human clinical trials involving the use of an innovative stem cell therapy to fight the virus that causes AIDS.

In a paper published in the May issue of the Journal of Virology, the UC Davis HIV team demonstrated both the safety and efficacy of transplanting anti-HIV stem cells into mice that represent models of infected patients. The technique, which involves replacing the immune system with stem cells engineered with a triple combination of HIV-resistant genes, proved capable of replicating a normally functioning human immune system by protecting and expanding HIV-resistant immune cells. The cells thrived and self-renewed even when challenged with an HIV viral load.

"We envision this as a potential functional cure for patients infected with HIV, giving them the ability to maintain a normal immune system through genetic resistance," said lead author Joseph Anderson, an assistant adjunct professor of internal medicine and a stem cell researcher at the UC Davis Institute for Regenerative Cures. "Ideally, it would be a one-time treatment through which stem cells express HIV-resistant genes, which in turn generate an entire HIV-resistant immune system."

To establish immunity in mice whose immune systems paralleled those of patients with HIV, Anderson and his team genetically modified human blood stem cells, which are responsible for producing the various types of immune cells in the body.

Building on work that members of the team have pursued over the last decade, they developed several anti-HIV genes that were inserted into blood stem cells using standard gene-therapy techniques and viral vectors (viruses that efficiently insert the genes they carry into host cells). The resulting combination vector contained:

These engineered blood stem cells, which could be differentiated into normal and functional human immune cells, were introduced into the mice. The goal was to validate whether this experimental treatment would result in an immune system that remained functional, even in the face of an HIV infection, and would halt or slow the progression toward AIDS.

The results were successful on all counts.

"After we challenged transplanted mice with live HIV, we demonstrated that the cells with HIV-resistant genes were protected from infection and survived in the face of a viral challenge, maintaining normal human CD4 levels," said Anderson. CD4+ T-cells are a type of specialized immune cell that HIV attacks and uses to make more copies of HIV.

"We actually saw an expansion of resistant cells after the viral challenge, because other cells which were not resistant were being killed off, and only the resistant cells remained, which took over the immune system and maintained normal CD4 levels," added Anderson.

The data provided from the study confirm the safety and efficacy of this combination anti-HIV lentiviral vector in a hematopoietic stem cell gene therapy setting for HIV and validated its potential application in future human clinical trials. The team has submitted a grant application for human clinical trials and is currently seeking regulatory approval, which is necessary to move on to clinical trials.

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Stem cell therapy to battle HIV?