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Skin layer grown from human stem cells could replace animals in drug and cosmetics testing

By Stem Cell Medical Center

PUBLIC RELEASE DATE:

24-Apr-2014

Contact: Jenny Gimpel jenny.gimpel@kcl.ac.uk 44-020-784-84334 King's College London

An international team led by King's College London and the San Francisco Veteran Affairs Medical Center (SFVAMC) has developed the first lab-grown epidermis the outermost skin layer - with a functional permeability barrier akin to real skin. The new epidermis, grown from human pluripotent stem cells, offers a cost-effective alternative lab model for testing drugs and cosmetics, and could also help to develop new therapies for rare and common skin disorders.

The epidermis, the outermost layer of human skin, forms a protective interface between the body and its external environment, preventing water from escaping and microbes and toxins from entering. Tissue engineers have been unable to grow epidermis with the functional barrier needed for drug testing, and have been further limited in producing an in vitro (lab) model for large-scale drug screening by the number of cells that can be grown from a single skin biopsy sample.

The new study, published in the journal Stem Cell Reports, describes the use of human induced pluripotent stem cells (iPSC) to produce an unlimited supply of pure keratinocytes the predominant cell type in the outermost layer of skin - that closely match keratinocytes generated from human embryonic stem cells (hESC) and primary keratinocytes from skin biopsies. These keratinocytes were then used to manufacture 3D epidermal equivalents in a high-to-low humidity environment to build a functional permeability barrier, which is essential in protecting the body from losing moisture, and preventing the entry of chemicals, toxins and microbes.

A comparison of epidermal equivalents generated from iPSC, hESC and primary human keratinocytes (skin cells) from skin biopsies showed no significant difference in their structural or functional properties compared with the outermost layer of normal human skin.

Dr Theodora Mauro, leader of the SFVAMC team, says: "The ability to obtain an unlimited number of genetically identical units can be used to study a range of conditions where the skin's barrier is defective due to mutations in genes involved in skin barrier formation, such as ichthyosis (dry, flaky skin) or atopic dermatitis. We can use this model to study how the skin barrier develops normally, how the barrier is impaired in different diseases and how we can stimulate its repair and recovery."

Dr Dusko Ilic, leader of the team at King's College London, says: "Our new method can be used to grow much greater quantities of lab-grown human epidermal equivalents, and thus could be scaled up for commercial testing of drugs and cosmetics. Human epidermal equivalents representing different types of skin could also be grown, depending on the source of the stem cells used, and could thus be tailored to study a range of skin conditions and sensitivities in different populations."

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Skin layer grown from human stem cells could replace animals in drug and cosmetics testing

Adult Stem Cell Research Shows Promise

By Stell Cell Research

Heba Degheidy, M.D., Ph.D., a post-doctoral research fellow at FDA, stores stem cell samples for analysis in an FDA laboratory on the National Institutes of Health (NIH) campus in Bethesda, Md.

Steven R. Bauer, Ph.D., chief of the Cellular and Tissue Therapy Branch in FDAs Office of Cellular Tissue and Gene Therapies (standing), visits his team of scientists in their lab.

For more photos of FDA's stem cell research team at work go to Flickr.

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Scientists sporting white coats and safety gloves are working in a bright Food and Drug Administration (FDA) lab on an incredible project.

They are part of FDAs MSC Consortium, a large team of FDA scientists studying adult mesenchymal stem cells (MSCs)cells that could eventually be used to repair, replace, restore or regenerate cells in the body, including those needed for heart and bone repair.

The scientistsinvestigational work is unprecedented: Seven labs at FDA's Center for Biologics Evaluation and Research formed the consortium to fill in gaps in knowledge about how stem cells function.

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Adult Stem Cell Research Shows Promise

Scientists Identify Cancer Specific Cell for Potential Targeted Treatment of Gastric Cancer

By Stem Cell Doctors

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Newswise A team of scientists led by a researcher from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore has identified the cancer specific stem cell which causes gastric cancer. This discovery opens up the possibility of developing new drugs for the treatment of this disease and other types of cancers.

The research group, led by Dr Chan Shing Leng, Research Assistant Professor at CSI Singapore, demonstrated for the first time that a cancer-specific variant of a cell surface protein, CD44v8-10, marks gastric cancer stem cells but not normal cells. Conceptualised by Dr Chan and Associate Professor Jimmy So, a Senior Consultant from the Department of Surgery at the National University Hospital Singapore, the study is also the first to be conducted with human gastric tissue specimens and took five years to complete. This novel study will be published in the research journal Cancer Research, the official journal of American Association of Cancer Research, in May 2014.

Gastric cancer is a major cause of cancer-related deaths worldwide, with low survival and high recurrence rates for patients with advanced disease. New therapies for the treatment of gastric cancer are urgently needed.

How CD44v8-10 serves as a biomarker

Many cancer cell types express high levels of a cell surface protein known as CD44. This protein marks cancer stem cells that are thought to be responsible for resistance to current cancer therapy and tumour relapse. There are many forms of CD44 and the standard form of CD44, CD44s, is found in high abundance on normal blood cells. It was previously not known which form of CD44 is found on cancer stem cells. This is critical as an ideal cancer target should mark only cancer cells but not normal cells.

Research by the team and other scientists in the field has led to the hypothesis that the growth of gastric cancer may be driven by cancer stem cells. In this study, the researchers analysed 53 patient tissue samples in conjunction with patient-derived xenograft models which are derived from intestinal type gastric cancer. The team is one of the few groups in the world to have a relatively large collection of patient-derived xenograft models for gastric cancer and the first to use these models for identification of gastric cancer stem cells. A total of eight cancer cell lines were used in this study, including six new cell lines which were established by the researchers.

The scientists discovered a cancer-specific CD44 variant, CD44v8-10 marks gastric cancer stem cells but not normal cells. CD44v8-10 promotes cancer cell growth and it is significantly more abundant in gastric tumour sites compared to normal gastric tissue, which makes it easily detectable. The findings results suggest that CD44v8-10 is an ideal target for developing clinical therapeutics against gastric cancer stem cells. As CD44v8-10 is cancer specific, it may also be used as a biomarker for screening and diagnosis of gastric cancer. This is significant as biomarkers for early detection of gastric cancer are currently not available and doctors rely on endoscopy for the screening and diagnosis of this disease.

Said Dr Chan, With our findings, we can now work on developing drugs that would recognise and attack the cancer stem cells only, reducing the side effects on normal cells. With additional funding, we aim to have a drug that can show efficacy in our models within three years.

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Scientists Identify Cancer Specific Cell for Potential Targeted Treatment of Gastric Cancer

Stem cells in circulating blood affect cardiovascular health, study finds

By Stem Cell Medicine

PUBLIC RELEASE DATE:

23-Apr-2014

Contact: Nicanor Moldovan Moldovan.6@osu.edu 614-247-7801 Ohio State University

COLUMBUS, Ohio New research suggests that attempts to isolate an elusive adult stem cell from blood to understand and potentially improve cardiovascular health a task considered possible but very difficult might not be necessary.

Instead, scientists have found that multiple types of cells with primitive characteristics circulating in the blood appear to provide the same benefits expected from a stem cell, including the endothelial progenitor cell that is the subject of hot pursuit.

"There are people who still dream that the prototypical progenitors for several components of the cardiovascular tree will be found and isolated. I decided to focus the analysis on the whole nonpurified cell population the blood as it is," said Nicanor Moldovan, senior author of the study and a research associate professor of cardiovascular medicine at The Ohio State University.

"Our method determines the contributions of all blood cells that serve the same function that an endothelial progenitor cell is supposed to. We can detect the presence of those cells and their signatures in a clinical sample without the need to isolate them."

The study is published in the journal PLOS ONE.

Stem cells, including the still poorly understood endothelial progenitor cells, are sought-after because they have the potential to transform into many kinds of cells, suggesting that they could be used to replace damaged or missing cells as a treatment for multiple diseases.

By looking at gene activity patterns in blood, Moldovan and colleagues concluded that many cell types circulating throughout the body may protect and repair blood vessels a key to keeping the heart healthy.

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Stem cells in circulating blood affect cardiovascular health, study finds

Stem Cells in Circulating Blood Affect Cardiovascular Health

By Stem Cell Medicine

Released: 4/21/2014 8:55 AM EDT Embargo expired: 4/23/2014 5:00 PM EDT Source Newsroom: Ohio State University Contact Information

Available for logged-in reporters only

Newswise COLUMBUS, Ohio New research suggests that attempts to isolate an elusive adult stem cell from blood to understand and potentially improve cardiovascular health a task considered possible but very difficult might not be necessary.

Instead, scientists have found that multiple types of cells with primitive characteristics circulating in the blood appear to provide the same benefits expected from a stem cell, including the endothelial progenitor cell that is the subject of hot pursuit.

There are people who still dream that the prototypical progenitors for several components of the cardiovascular tree will be found and isolated. I decided to focus the analysis on the whole nonpurified cell population the blood as it is, said Nicanor Moldovan, senior author of the study and a research associate professor of cardiovascular medicine at The Ohio State University.

Our method determines the contributions of all blood cells that serve the same function that an endothelial progenitor cell is supposed to. We can detect the presence of those cells and their signatures in a clinical sample without the need to isolate them.

The study is published in the journal PLOS ONE.

Stem cells, including the still poorly understood endothelial progenitor cells, are sought-after because they have the potential to transform into many kinds of cells, suggesting that they could be used to replace damaged or missing cells as a treatment for multiple diseases.

By looking at gene activity patterns in blood, Moldovan and colleagues concluded that many cell types circulating throughout the body may protect and repair blood vessels a key to keeping the heart healthy.

The scientists also found that several types of blood cells retain so-called primitive properties. In this context, primitive is positive because these cells are the first line of defense against an injury and provide a continuous supply of repair tissue either directly or by telling local cells what to do.

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Stem Cells in Circulating Blood Affect Cardiovascular Health

Stress Could Activate "Crosstalking" Cell Signals That Turn Bodys Natural Wound Healing Process Against It

By Uncategorized

Durham, NC (PRWEB) April 23, 2014

Stress could activate "crosstalking" cell signals that decrease the bodys natural healing process after a wound occurs, according to a new study released today in STEM CELLS Translational Medicine. The finding helps explain how stress impairs healing and, conversely, could lead to a way to overcome chronic wounds resulting from serious burns and other skin injuries.

Chronic wounds are a major global health problem, with annual costs in the United States alone of more than $23 billion, said Roslyn Isseroff, M.D., of the University of California Davis and the Northern California Health Care Systems Department of Veterans Affairs. She was a lead investigator in the study along with Mohan R. Dasu, Ph.D.

The precise process that prevents their healing is unclear except for two constants: a prolonged inflammatory response and the bacterial colonization of the wound bed. These two interrelated factors are thought to contribute to the wounds chronic state.

Previous studies had demonstrated an increase in epinephrine (adrenaline), as occurs during stress, produces an increase in the activity of TLR2 (Toll-like receptor 2), a protein that appears to stimulate the early inflammatory process needed to set the steps of healing in motion. Together they alter the ability of stem cells and keratinocytes, the barrier-forming cells that make up 90 percent of skin, to repair wound damage by slowing down the stem cells migration to the area and by promoting inflammation.

To compound the potential for damage, bacteria in the wound can activate the TLR2 system, and crosstalk to the epinephrine signaling system, creating a cycle of escalating damaging signals.

The Isseroff and Dasu team, which included colleagues at UC-Daviss Institute for Regenerative Cures and California State University, decided to look at how increased epinephrine and TLR2 stimulation affected stem cells taken from bone marrow and keratinocytes by analyzing the "crosstalk" between their signaling pathways. The researchers tested their theory in cultured cells and in mice. In both instances they found that the crosstalk led to impaired healing, with elevated levels of TLR2 as well as MyD88 and IL-6, both of which regulate the activation of numerous pro-inflammatory genes, in the wounds.

Thus, our data describe a recipe for decreasing cell migration and exacerbating inflammation via novel crosstalk between the adrenergic and Toll-like receptor pathways in wounds, Dr. Dasu said.

"These findings have implications for understanding the mechanisms controlling the differing susceptibility to infections and immune/inflammatory-related conditions in wounds," said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

The full article, Crosstalk Between Adrenergic and Toll-Like Receptors in Human Mesenchymal Stem Cells and Keratinocytes: A Recipe for Impaired Wound Healing, can be accessed at http://www.stemcellstm.com.

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Stress Could Activate "Crosstalking" Cell Signals That Turn Bodys Natural Wound Healing Process Against It

Autologous stem cell therapy improves motor function in chronic stroke victims

By Uncategorized

PUBLIC RELEASE DATE:

23-Apr-2014

Contact: Robert Miranda cogcomm@aol.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (Apr. 23, 2014) People who have had a stroke, often suffer motor deficits with little potential to restore neurological function. However, a study conducted in Taiwan, that will be published in a future issue of Cell Transplantation, but is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-ct1168Chen, has found that when one group of stroke victims had their own peripheral blood stem cells (PBSCs) injected directly into the brain and a similar group did not, those who received the PBSCs experienced some "improvement in stroke scales and functional outcome." Those in the PBSC-injected group also received injections of the growth factor granulocyte-colony stimulating factor (G-CSF), known to be potentially neuroprotective.

"In this phase 2 study, we provide the first evidence that intracerebral injection of autologous (self-donated) PBSCs can improve motor function in those who have suffered a stroke and have motor deficits as a result," said study corresponding Dr. Woei-Cheng Shyu of the Center for Neuropsychiatry, Graduate Institute of Immunology and Translational Medicine Research Center, China Medical University in Taiwan. "Our study demonstrated that this therapeutic strategy was feasible and safe in stroke patients who suffered a prior stroke, but within five years from the onset of symptoms."

According to the authors, there has been little advance made in restoring neurological function following ischemic stroke. However, since neuronal death is the primary mechanism that limits functional recovery, stem cell therapy is emerging as a potentially effective regenerative approach. Once more PBSCs are being increasingly used as a self-donated source for cell therapies for regenerating skeletal muscle, heart and neurons. The PBSCs may need to be "amplified" with G-CSF, speculated the researchers.

All of the patients in the trial had suffered a stroke in the past, as long as five years prior to this study. At the end of a 12 month follow-up, the group of 15 patients with neurological deficits who received injections of PBSCs experienced neurological and functional improvement based on a number of clinical outcomes measures. The control group of 15 patients with neurological deficits that did not receive the PBSC injections did not experience the same beneficial outcomes.

The researchers reported that nine of the 15 patients undergoing PBSC transplantation experienced "positive motor evoked potentials" (MEPs) after transcranial magnetic stimulation, but why MEPs appeared in some of the transplanted group, but not all, was unclear.

"Despite this success, it should be noted that this was a preliminary study and, due to the small number of patients, are tentative," concluded the researchers. "In the future we plan to conduct a multi-center, large-scale, double blind, placebo-controlled randomized studies to better evaluate the effect of PBSC implantation in patients suffering from the effects of past stroke."

"This phase II study offers pilot clinical evidence supporting the use of autologous stem cell-based treatment for stroke" said Dr. Cesar V. Borlongan, Prof. of Neurosurgery and Director of the Center of Excellence for Aging & Brain Repair at the University of South Florida. "Clarification of the impact of G-CSF on the cells and whether other factors are necessary to maximize the benefit of cell transplantation, as well as further studies with a larger number of patients are necessary to determine equivocal safety and efficacy of this treatment".

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Autologous stem cell therapy improves motor function in chronic stroke victims

Miami Stem Cell Treatment Center Visits the Forum at Deer Creek: Senior Living Center

By Stem Cell Treatment

Deerfield Beach, Florida (PRWEB) April 23, 2014

The Miami Stem Cell Treatment Center, PC, located in Miami, Ft. Lauderdale, and Boca Raton, Florida, announces their invite to speak at the Forum at Deer Creek in Deerfield, Florida on the use of stem cells for various degenerative and inflammatory conditions. This will be provided by Dr. Nia Smyrniotis, Medical Director.

This seminar will be held on April 28 at 2:30 pm at the Forum at Deer Creek, 3001 Deer Creek Country Club Blvd., Deerfield Beach, FL 33442.

At the Miami Stem Cell Treatment Center, utilizing investigational protocols, adult adipose derived stem cells (ADSCs) can be deployed to improve patients quality of life with a number of degenerative conditions and diseases. ADSCs are taken from the patients own adipose (fat) tissue (also called stromal vascular fraction (SVF). Adipose tissue is exceptionally abundant in ADSCs. The adipose tissue is obtained from the patient during a 15 minute mini-liposuction performed under local anesthesia in the doctors office. SVF is a protein-rich solution containing mononuclear cell lines (predominantly autologous mesenchymal stem cells), macrophage cells, endothelial cells, red blood cells, and important Growth Factors that facilitate the stem cell process and promote their activity.

ADSCs are the body's natural healing cells - they are recruited by chemical signals emitted by damaged tissues to repair and regenerate the bodys damaged cells. The Miami Stem Cell Treatment Center only uses autologous stem cells from a person's own fat no embryonic stem cells are used. Our current areas of study include: heart failure, emphysema, COPD, asthma, Parkinsons disease, stroke, multiple sclerosis, and orthopedic joint injections. For more information, or if someone thinks they may be a candidate for one of the stem cell protocols offered by Miami Stem Cell Treatment Center, they may contact Dr. Nia Smyrniotis directly at (561) 331-2999, or see a complete list of the Centers study areas at: http://www.MiamiStemCellsUSA.com.

About Miami Stem Cell Treatment Center:

The Miami Stem Cell Treatment Center is an affiliate of the Cell Surgical Network (CSN). We provide care for people suffering from diseases that may be alleviated by access to adult stem cell based regenerative treatment. We utilize a fat transfer surgical technology to isolate and implant the patients own stem cells from a small quantity of fat harvested by a mini-liposuction on the same day. The investigational protocols utilized by the Miami Stem Cell Treatment Center have been reviewed and approved by an IRB (Institutional Review Board) which is registered with the U.S. Department of Health, Office of Human Research Protections (OHRP) and the study is registered with Clinicaltrials.gov, a service of the U.S. National Institutes of Health (NIH). For more information contact: Info(at)MiamiStemCellsUSA(dot)com or visit our website: http://www.MiamiStemCellsUSA.com.

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Miami Stem Cell Treatment Center Visits the Forum at Deer Creek: Senior Living Center

Irvine Stem Cell Treatment Center: Upcoming Lecture at Thousand Oaks Library

By Stem Cell Treatment

Thousand Oaks, CA (PRWEB) April 23, 2014

The Irvine Stem Cell Treatment Center, PC, located in Irvine, California, announces a free public seminar on the use of stem cells for various degenerative and inflammatory conditions. They will be provided by Dr. Thomas A. Gionis, Surgeon-in-Chief.

The seminar will be held on Tuesday, April 29th at 4:00 p.m. and 7:00 p.m. at the Thousand Oaks Library, 1401 E. Janss Road, Thousand Oaks, CA.

At the Irvine Stem Cell Treatment Center, utilizing investigational protocols, adult adipose derived stem cells (ADSCs) can be deployed to improve patients quality of life with a number of degenerative conditions and diseases. ADSCs are taken from the patients own adipose (fat) tissue (also called stromal vascular fraction (SVF)). Adipose tissue is exceptionally abundant in ADSCs. The adipose tissue is obtained from the patient during a 15 minute mini-liposuction performed under local anesthesia in the doctors office. SVF is a protein-rich solution containing mononuclear cell lines (predominantly autologous mesenchymal stem cells), macrophage cells, endothelial cells, red blood cells, and important Growth Factors that facilitate the stem cell process and promote their activity.

ADSCs are the body's natural healing cells - they are recruited by chemical signals emitted by damaged tissues to repair and regenerate the bodys damaged cells. The Irvine Stem Cell Treatment Center only uses autologous stem cells from a person's own fat no embryonic stem cells are used. Our current areas of study include: Heart Failure, Emphysema, COPD, Asthma, Parkinsons Disease, Stroke, Multiple Sclerosis, and orthopedic joint injections. For more information, or if someone thinks they may be a candidate for one of the stem cell protocols offered by Irvine Stem Cell Treatment Center, they may contact Dr. Gionis directly at (949) 679-3889, or see a complete list of the Centers study areas at: http://www.StemCellsUSA.net.

About Irvine Stem Cell Treatment Center: The Irvine Stem Cell Treatment Center is an affiliate of the Cell Surgical Network (CSN). We provide care for people suffering from diseases that may be alleviated by access to adult stem cell based regenerative treatment. We utilize a fat transfer surgical technology to isolate and implant the patients own stem cells from a small quantity of fat harvested by a mini-liposuction on the same day. The investigational protocols utilized by the Irvine Stem Cell Treatment Center have been reviewed and approved by an IRB (Institutional Review Board) which is registered with the U.S. Department of Research Protections; and the study is registered with Clinicaltrials.gov, a service of the U.S. National Institutes of Health (NIH). For more information contact: Info(at)StemCellsUSA(dot)net or visit our website: http://www.StemCellsUSA.net.

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Irvine Stem Cell Treatment Center: Upcoming Lecture at Thousand Oaks Library

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