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Category Archives: New Jersey Stem Cells
EAT A PEACH | Beneficial Bacteria
Posted: April 7, 2015 at 6:56 pm
By ELLA NONNI
In the past decade, bacteria have gone from infectious pests to digestion aiding assets. It is common knowledge that yogurt is good for an upset stomach, or that you should eat yogurt while taking antibiotics, but now probiotic supplements have an entire section in every drugstore, and innovative, probiotic-rich foods like kombucha and kefir are increasing in popularity. Bacteria were first discovered as the culprits of disease, and since then, we have spent the majority of our scientific history studying the pathogens. Only recently have we begun to uncover the major role beneficial bacteria play in our body systems, and it turns out their significance is unparalleled.
A Complex Ecosystem
We used to think that the body itself was capable of carrying out all its functions as an independent organism. Now were discovering that is a far cry from reality. Science writer Jennifer Ackerman explains, [The body] is more like a complex ecosystem a social network containing trillions of bacteria and other microorganisms that inhabit our skin, genital areas, mouth and especially intestines. Most cells in the human body are not human cells at all; in any given individual, bacterial cells outnumber human cells 10 to one. Latest research suggests that in the human digestive system alone there are over 1,000 bacterial species, comprising over 3.3 million genes 150 times the total number of genes in the human body. The Human Genome Project revealed that all humans share 99.9% of their DNA, giving us little basis to explain why individuals and populations appear to vary so greatly. One explanation may be the variations in our microbial makeup, which influence our digestion, immunity, reproduction and behavior.
We spent hundreds of thousands of years evolving as humans, but we were not only adjusting to our environments we were adjusting in order to live in harmony with the microorganisms in them. We are at the point where our bodies could not carry out functions necessary for survival without the aid of these symbionts. With the advent and rapid rise in antibiotic use, we have inadvertently disrupted our microbial communities, and therefore our entire bodys homeostasis. We are just beginning to understand how current health crises, such as obesity and autoimmune disorders, may be influenced by this disruption.
Obesity
Probiotic bacteria do more than just synthesize vitamins and break down indigestible foods they also play a major role in the regulation of appetite. The bacterium Helicobactor pylori, for example, is a commensal that was previously demonized as a pathogen for its role in the development peptic ulcers in susceptible individuals. Not only does H. pylori actually regulate stomach acid levels, but it is involved in regulating ghrelin, the hormone responsible for hunger. Researchers are still not sure how it does this, but in persons with no H. pylori, ghrelin levels do not decrease after eating like they are supposed to. Consequently, these individuals experience prolonged hunger, and in studies, gained significantly more weight than those who had the bacterium in their gastric flora. A few generations ago (before the advent of antibiotics), more than 80% of Americans were hosts to H. pylori. Now less than 6% of American children test positive. Most children in the U.S. have been on antibiotics multiple times by the age of 15 for various common illnesses like ear infections and strep. Some researchers theorize that widespread use of antibiotics in children (and thus the elimination of bacteria like H. pylori) helps to explain the rising rates of childhood obesity. Microorganisms also assist in the transformation of stem cells into fat, muscle or bone cells during child development. Interrupting the bacteria that aid this process may be causing the overproduction of fat cells (and underproduction of bone and muscle).
Finally, antibiotics themselves, as livestock farmers know, accelerate weight gain. In her New York Times article, Pagan Kennedy claims that decades of agricultural research have shown that antibiotics seem to flip a switch in young animals bodies, helping them pack on pounds. In the 1950s, scientists fed antibiotics to schoolchildren in Guatemala for over a year. The group supplemented with antibiotics gained an average of 6.5 lbs per year while the control group averaged 1.9 lbs. This antibiotic effect is especially potent when the drugs are combined with calorie-dense foods, which are more available than ever before in the United States.
Autoimmune disorders
Even our immune systems require the assistance of commensal bacteria in order to function properly. Its rather ironic the immune system, whose goal is to detect and eliminate harmful bacteria, can only function with the help of other non-harmful bacteria. The bacterium Bacteroides fragilis, for instance, regulates the balance between pro-inflammatory and anti-inflammatory T cells. The immune systems of mice withoutB. fragilis were defective, and their regulatory T cells underperformed. When B. fragilis was reintroduced, immune function was restored.
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ADDING MULTIMEDIA FDA Expands Indication for REVLIMID (Lenalidomide) in Combination with Dexamethasone to Include …
Posted: February 19, 2015 at 10:56 pm
SUMMIT, N.J.--(BUSINESS WIRE)--Celgene Corporation (NASDAQ:CELG) today announced that the U.S. Food and Drug Administration (FDA) has expanded the existing indication for REVLIMID (lenalidomide) in combination with dexamethasone to include patients newly diagnosed with multiple myeloma (NDMM). REVLIMID plus dexamethasone was previously approved in June 2006 for use in multiple myeloma patients who have received at least one prior therapy.
The approval of REVLIMID as an option for use in all patients with multiple myeloma represents a new paradigm in the management of this disease, said Kenneth Anderson, M.D., Director, Jerome Lipper Multiple Myeloma Center, Dana-Farber/Brigham and Womens Cancer Center. We now have clinical evidence demonstrating that starting and keeping newly diagnosed multiple myeloma patients on REVLIMID significantly improves progression-free survival.
The approval was based on safety and efficacy results from phase III studies, including the FIRST trial (MM-020/IFM 07-01), which evaluated continuous REVLIMID in combination with dexamethasone (Rd Continuous) until disease progression versus melphalan, prednisone and thalidomide (MPT) for 18 months as the primary analysis, and a fixed duration of 18 cycles of Rd (Rd18) as a secondary analysis, in 1,623 newly diagnosed patients who were not candidates for stem cell transplant.
In this randomized, open-label, three-arm trial, median progression-free survival (PFS), the length of time a patient lives from study randomization to disease progression or death was the primary endpoint of the study. PFS was significantly longer for patients receiving Rd Continuous (25.5 months) than for those treated with MPT (21.2 months; HR=0.72; p=0.0001). Median overall survival (OS) in the two groups was 58.9 months and 48.5 months, respectively (HR 0.75; 95% CI 0.62, 0.90) based on a March 3, 2014 interim OS analysis. Patients in the Rd Continuous arm had a 25% reduction in the risk of death compared to patients in the MPT arm.
Safety results showed that adverse reactions reported in 20% of NDMM patients in the Rd Continuous, Rd18 or MPT arms included diarrhea (45.5%, 38.5%, 16.5%), anemia (43.8%, 35.7%, 42.3%), neutropenia (35.0%, 33.0%, 60.6%), fatigue (32.5%, 32.8%, 28.5%), back pain (32.0%, 26.9%, 21.4%), insomnia (27.6%, 23.5%, 9.8%), asthenia (28.2%, 22.8%, 22.9%), rash (26.1%, 28.0%, 19.4%), decreased appetite (23.1%, 21.3%, 13.3%), cough (22.7%, 17.4%, 12.6%), pyrexia (21.4%, 18.9%, 14.0%), muscle spasms (20.5%, 18.9%, 11.3%) and abdominal pain (20.5%, 14.4%, 11.1%).
The most frequently reported Grade 3 or 4 events in the Rd Continuous arm (until disease progression) included neutropenia (27.8%), anemia (18.2%), thrombocytopenia (8.3%), pneumonia (11.3%), asthenia (7.7%), fatigue (7.3%), back pain (7%), hypokalemia (6.6%), rash (7.3%), cataract (5.8%), dyspnea (5.6%), DVT (5.6%) and hyperglycemia (5.3%).
At Celgene, we are very happy with the FDAs decision, which adds information on the use of REVLIMID plus dexamethasone as a first-line treatment for multiple myeloma to the prescribing information, said Jacqualyn A. Fouse, Ph.D., President, Global Hematology and Oncology for Celgene. Now, as part of our commitment to improving the lives of patients living with this disease, our next step is to make the benefits of this treatment regimen available to those now eligible under the expanded indication.
Celgene currently has an application under review with the European Medicines Agency (EMA) for approval to use REVLIMID for the treatment of adult patients with previously untreated multiple myeloma who are not eligible for transplant. The EMAs Committee for Medicinal Products for Human Use (CHMP) published a positive opinion for this application in December 2014.
About REVLIMID
In the United States, REVLIMID is approved in combination with dexamethasone for the treatment of patients with multiple myeloma. REVLIMID is also approved in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy in nearly 70 countries, encompassing Europe, the Americas, the Middle East and Asia, and in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy in Australia and New Zealand.
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FDA Expands Indication for REVLIMID (Lenalidomide) in Combination with Dexamethasone to Include Patients Newly …
Posted: February 18, 2015 at 10:57 pm
SUMMIT, N.J.--(BUSINESS WIRE)--Celgene Corporation (NASDAQ:CELG) today announced that the U.S. Food and Drug Administration (FDA) has expanded the existing indication for REVLIMID (lenalidomide) in combination with dexamethasone to include patients newly diagnosed with multiple myeloma (NDMM). REVLIMID plus dexamethasone was previously approved in June 2006 for use in multiple myeloma patients who have received at least one prior therapy.
The approval of REVLIMID as an option for use in all patients with multiple myeloma represents a new paradigm in the management of this disease, said Kenneth Anderson, M.D., Director, Jerome Lipper Multiple Myeloma Center, Dana-Farber/Brigham and Womens Cancer Center. We now have clinical evidence demonstrating that starting and keeping newly diagnosed multiple myeloma patients on REVLIMID significantly improves progression-free survival.
The approval was based on safety and efficacy results from phase III studies, including the FIRST trial (MM-020/IFM 07-01), which evaluated continuous REVLIMID in combination with dexamethasone (Rd Continuous) until disease progression versus melphalan, prednisone and thalidomide (MPT) for 18 months as the primary analysis, and a fixed duration of 18 cycles of Rd (Rd18) as a secondary analysis, in 1,623 newly diagnosed patients who were not candidates for stem cell transplant.
In this randomized, open-label, three-arm trial, median progression-free survival (PFS), the length of time a patient lives from study randomization to disease progression or death was the primary endpoint of the study. PFS was significantly longer for patients receiving Rd Continuous (25.5 months) than for those treated with MPT (21.2 months; HR=0.72; p=0.0001). Median overall survival (OS) in the two groups was 58.9 months and 48.5 months, respectively (HR 0.75; 95% CI 0.62, 0.90) based on a March 3, 2014 interim OS analysis. Patients in the Rd Continuous arm had a 25% reduction in the risk of death compared to patients in the MPT arm.
Safety results showed that adverse reactions reported in 20% of NDMM patients in the Rd Continuous, Rd18 or MPT arms included diarrhea (45.5%, 38.5%, 16.5%), anemia (43.8%, 35.7%, 42.3%), neutropenia (35.0%, 33.0%, 60.6%), fatigue (32.5%, 32.8%, 28.5%), back pain (32.0%, 26.9%, 21.4%), insomnia (27.6%, 23.5%, 9.8%), asthenia (28.2%, 22.8%, 22.9%), rash (26.1%, 28.0%, 19.4%), decreased appetite (23.1%, 21.3%, 13.3%), cough (22.7%, 17.4%, 12.6%), pyrexia (21.4%, 18.9%, 14.0%), muscle spasms (20.5%, 18.9%, 11.3%) and abdominal pain (20.5%, 14.4%, 11.1%).
The most frequently reported Grade 3 or 4 events in the Rd Continuous arm (until disease progression) included neutropenia (27.8%), anemia (18.2%), thrombocytopenia (8.3%), pneumonia (11.3%), asthenia (7.7%), fatigue (7.3%), back pain (7%), hypokalemia (6.6%), rash (7.3%), cataract (5.8%), dyspnea (5.6%), DVT (5.6%) and hyperglycemia (5.3%).
At Celgene, we are very happy with the FDAs decision, which adds information on the use of REVLIMID plus dexamethasone as a first-line treatment for multiple myeloma to the prescribing information, said Jacqualyn A. Fouse, Ph.D., President, Global Hematology and Oncology for Celgene. Now, as part of our commitment to improving the lives of patients living with this disease, our next step is to make the benefits of this treatment regimen available to those now eligible under the expanded indication.
Celgene currently has an application under review with the European Medicines Agency (EMA) for approval to use REVLIMID for the treatment of adult patients with previously untreated multiple myeloma who are not eligible for transplant. The EMAs Committee for Medicinal Products for Human Use (CHMP) published a positive opinion for this application in December 2014.
About REVLIMID
In the United States, REVLIMID is approved in combination with dexamethasone for the treatment of patients with multiple myeloma. REVLIMID is also approved in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy in nearly 70 countries, encompassing Europe, the Americas, the Middle East and Asia, and in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy in Australia and New Zealand.
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FDA Expands Indication for REVLIMID (Lenalidomide) in Combination with Dexamethasone to Include Patients Newly ...
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New Jersey Commission Science and Technology Grants – Stem …
Posted: February 13, 2015 at 3:55 pm
Martin Grumet, Ph.D. Professor, Department of Cell Biology and Neuroscience Director, W.M. Keck Center for Collaborative Neuroscience Rutgers Stem Cell Research Center
Modulation of recovery from neural trauma by neural stem cells
Neural stem cells give rise to neurons and glia during development providing most of the cells that form the nervous system but very few stem cells persist in the adult brain. Transplantation of neural stem and progenitor cells into the injured central nervous system is a promising approach to promote repair and recovery after injury. Towards that goal, we are analyzing the development of different kinds of neural cells that can be derived from embryonic stem (ES) cells in the laboratory and testing their behavior after transplantation into the injured nervous system.
Ronald P. Hart, Ph.D. Professor, Department of Cell Biology and Neuroscience W.M. Keck Center for Collaborative Neuroscience Rutgers Stem Cell Research Center
Regulation of microRNA gene expression in differentiating neural stem cells
The key to transforming human stem cells into therapeutic transplants is the faithful control of differentiation the process by which cells acquire specialized functions during embryogenesis in the culture dish. A newly-discovered class of regulatory molecules, known as microRNAs, has been discovered to be required for stem cell differentiation. Our experiments will help to define groups of microRNAs that are regulated during neurogenesis and how they work to control production of neurons or non-neuronal cells in the nervous system. We propose that addition of artificial microRNA molecules will help control differentiation of stem cells prior to transplant, helping to guide the differentiation process towards cell types that are desired and away from products that are unwanted, and enhancing the utility and safety of therapeutic stem cells.
Melitta Schachner, Ph.D. Research Professor II New Jersey Professor of Spinal Cord Research W.M. Keck Center for Collaborative Neuroscience Department of Cell Biology and Neuroscience
Therapeutic use of genetically engineered human ES cells overexpressing the neural cell adhesion molecule L1
My research focuses on recognition molecules found on or near the surface of nerve cells. These molecules tell cells whether they can bind together, an activity important in repairing damaged nervous system tissue. The neural cell adhesion molecule L1 regulates brain development by promoting contacts between nerve cells, thus generating a functional nervous system. Its beneficial influence is important for regeneration after trauma, for example, in spinal cord injury or Huntington's and Parkinson's diseases. When overexpressed in mouse ES cells, L1 enhances survival of imperiled host nerve cells, makes the overexpressing stem cells migrate better in the host tissue, and helps form connections between the transplanted stem cells and the host leading to functional recovery. Important also is its ability to halt tumor formation. We are working toward developing human ES cell lines which overexpress L1, monitor their beneficial potential, and expand their therapeutic potential.
Jay A. Tischfield, Ph.D., FACMG Duncan and Nancy MacMillan Prof of Genetics & Chair (Prof of Pediatrics and Psychiatry, Robert Wood Johnson Medical School, UMDNJ) Rutgers University Cell and DNA Repository
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Stem Cells from Placenta Show Promise for Treating Heart Failure
Posted: February 12, 2015 at 5:59 am
Durham, NC (PRWEB) February 11, 2015
Stem cells collected from placenta, which is generally discarded after childbirth, show promise as a treatment for heart failure. Found in the latest issue of STEM CELLS Translational Medicine, a new study using mice determined that human-derived adherent cells (PDAC cells) significantly improved cardiac function when injected into the heart muscle.
Currently, about 6 million people in the United States alone suffer from heart failure, which is when the hearts pumping power is weaker than normal. Despite intensive medical care, almost 80 percent of people die within eight years of diagnosis, making it the worlds leading cause of death. Heart failure can be the result of coronary artery disease, heart attack and other conditions such as high blood pressure and valve disease.
Cell therapies for cardiac repair have generated considerable interest in recent years. While earlier studies using autologous bone marrow transplantation (that is, stem cells collected from the patients own bone marrow) helped improve cardiac function after myocardial infarction (MI), more recent studies showed no benefit in the early stages after MI. This has led researchers to question whether mesenchymal stem cells from sources other than bone marrow, such as cord blood and placenta tissue, might yield better results.
Among those interested in this is an international team co-led by Patrick C.H. Hsieh of Taiwans Institute of Biomedical Sciences, Academia Sinica, Taipei, and Uri Herzberg of Celgene Cellular Therapeutics, Warren, New Jersey, U.S. They recently undertook a study to test the therapeutic effects of PDA-001, an intravenous formulation of PDAC cells, in mice. The researchers were also testing the best way to deliver the therapy.
Three weeks after chronic heart failure was induced in the animals they were treated with the stem cells by either direct intramyocardial (IM) or intravenous (IV) injection, Dr. Hsieh said. The results showed that the IM injections significantly improved the left ventricle systolic and diastolic functions compared with injection of vehicle or IV injection of PDA-001.
The IM injections also decreased cardiac fibrosis in the vicinity of the injection sites. We repeatedly observed improvement of cardiac function in the injected sites following IM PDA-001 treatment, Dr. Herzberg added. Based on these results, we want to continue our investigations to optimize the effect through controlling the dose, timing and delivery.
In this animal model of progressive heart injury, stem cells isolated from placenta showed promise as an off-the-shelf therapy for cardiac repair, warranting the need for testing in additional models," said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.
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The full article, Human Placenta-derived Adherent Cells Improve Cardiac Performance in Mice with Chronic Heart Failure, can be accessed at http://stemcellstm.alphamedpress.org/content/early/2015/02/09/sctm.2014-0135.full.pdf+html.
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A Few Cells Could Prevent Bone Marrow Transplant Infections
Posted: February 3, 2015 at 7:07 pm
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Newswise (PHILADELPHIA) Bone marrow transplantation is a life-saving therapy for patients with blood cancers like leukemia or lymphoma. However, the depletion of the patients immune system prior to transplantation can put patients at risk of for an infection by a virus called cytomegalovirus (CMV) that can be life threatening in these immune-compromised individuals. Now, researchers have found that a very small subset of anti-viral immune cells, transplanted along with a donors blood stem cells, could be enough to fight and even prevent the disease caused by CMV, in research conducted in mice and published Jan 16th in the Journal of Immunology.
Anywhere between 50-80 percent of adults in the United States are infected with CMV, although the virus is kept under control by a healthy immune system. In patients with weakened immune systems, however, CMV can become reactivated and can cause life-threatening pneumonia, among other symptoms. Current treatment includes antiviral medication, but these are not always well tolerated by patients and they also harm the very cells that bone marrow transplantation aims to replenish.
We know that re-establishment of anti-viral immunity in these patients is critical to fully control cytomegalovirus in bone marrow transplant recipients, says senior author Christopher Snyder, Ph.D., an Assistant Professor of Microbiology and Immunology at Thomas Jefferson University. Our study suggests that, in addition to infusing stem cells that restore the bone marrow, life-long anti-CMV immunity may be rapidly restored by also infusing a subset of anti-viral immune cells that have stem cell-like properties.
Currently, investigators around the world are experimenting with restoring the immune cells responsible for keeping CMV in check by transplanting those specific anti-viral cells from healthy donors a type of immunotherapy. The problem, says Dr. Snyder, is that current methods for selecting anti-viral immune cells may inadvertently limit the ability of those cells to restore life-long immunity.
To date, researchers have focused on developing anti-CMV immunotherapy around the fighter cells called CD8 T effector cells that attack and kill virally-infected host cells. These cells are selected and expanded in the lab to increase their numbers, but this process may limit their life-span and ability to divide.
Dr. Snyder and colleagues found that CMV-specific fighter T cells divided poorly in response to CMV infection or reactivation in mouse models. They hypothesized that a different type of CD8 T cells one that acts more like a stem cell could help control the infection long term. His group showed that a small number of stem-cell like CD8 T cells called memory cells were enough to produce and repeatedly replenish all of the T-effector cells needed to fight the disease. The infused memory cells became major contributors to the recipient anti-viral immune response, persisting for at least 3 months of time and producing the "fighter" cells at a steady stream.
In order to survey whether these cells have counterparts in humans, the researchers compared the genomic fingerprint the profile of genes that were turned up or down of mouse and human memory T cells that were specific for CMV and found that the two had similar profiles. This suggested that human and mouse CMV-specific memory T cells are very similar populations. Therefore infusing similar cells into humans could improve on immunotherapeutic methods for controlling CMV infection," said first author Michael Quinn MD/PhD student in the Department of Microbiology and Immunology at Thomas Jefferson University. This may be a valuable approach to keep the disease from emerging in people.
Our data argue for developing new clinical trials focused specifically on using these T memory cells, in order to determine if it would indeed be better than current therapeutic options, said Dr. Snyder.
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A Few Cells Could Prevent Bone Marrow Transplant Infections
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Dynamic Imaging System Nets Yale Scientist the 2014 STEM CELLS Young Investigator Award
Posted: December 4, 2014 at 5:54 pm
Durham, NC (PRWEB) December 04, 2014
Shangqin Guo, Ph.D., a scientist at Yale University, is the recipient of the 2014 STEM CELLS Young Investigator Award. The award is presented to a young researcher who serves as principal author of a significant study published in the journal over the past year.
The paper that earned Dr. Guo this recognition is "Dynamic Migration and Cell-Cell Interactions of Early Reprogramming Revealed by High Resolution Time-Lapse Imaging, published in STEM CELLS May 2013 issue. It describes a live cell imaging approach for studying the process of Yamanaka reprogramming at single cell resolution. It also reports on the unexpected dynamic behaviors associated with early reprogramming and explores how such behaviors could compromise conventional experimental designs and interfere with data interpretation.
Jan A. Nolta, Ph.D., editor-in-chief of STEM CELLS, commented on Dr. Guos award. There are still many questions about how cells can be most effectively reprogrammed back to pluripotency and what steps occur during this process, she said. The outstanding study by Dr. Guos laboratory created a dynamic imaging system that was used to address multiple key questions regarding early reprogramming from hematopoietic cells.
The studies show the importance of cell-to-cell contact through dumbbell structures after early divisions and identify E-cadherin as a key regulator. The use of the imaging and new technology in this study is truly elegant, and I congratulate our Young Investigator Award winner on this important accomplishment, she added.
Dr. Guo currently is assistant professor in the Department of Cell Biology at Yale University. Her lab at the Yale Stem Cell Center focuses on learning the cell fate decision processes including how does a cell know what to be and what not to be?
For someone who is just starting off, this provides a sense of reassurance, recognition and gratification, she said about receiving the award.
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Full Citation: Megyola, C. M., Gao, Y., Teixeira, A. M., Cheng, J., Heydari, K., Cheng, E.-C., Nottoli, T., Krause, D. S., Lu, J. and Guo, S. (2013), Dynamic Migration and Cell-Cell Interactions of Early Reprogramming Revealed by High-Resolution Time-Lapse Imaging. STEM CELLS, 31: 895905. doi: 10.1002/stem.1323
Paper URL: http://onlinelibrary.wiley.com/doi/10.1002/stem.1323/full
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Targeting cancer stem cells: a new therapy to cure cancer …
Posted: October 29, 2014 at 3:07 am
Am J Cancer Res. 2012; 2(3): 340356.
Published online Apr 28, 2012.
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, China
Received April 20, 2012; Accepted April 25, 2012.
Cancer stem cells (CSCs) have been defined as cells within tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. They have been identified in blood, breast, brain, colon, melanoma, pancreatic, prostate, ovarian, lung cancers and so on. It is often considered to be associated with chemo-resistance and radio-resistance that lead to the failure of traditional therapies. Most therapies are directed at the fast growing tumor mass but not the slow dividing cancer stem cells. Eradicating cancer stem cells, the root of cancer origin and recurrence, has been thought as a promising approach to improve cancer survival or even to cure cancer patients. Understanding the characteristics of cancer stem cells will help to develop novel therapies to eliminate the initiating cancer stem cell, and the relevant patents on the cancer stem cell and cancer therapy by cancer stem cells will be discussed.
Keywords: Cancer stem cell, biomarker, signal pathway, drug resistance, natural compound, Mesenchymal stem cells, differentiation therapy
In the world, cancer remains a major cause of mortality. Despite great progresses have been made in understanding the molecular basis of cancer, the progress in cancer detection and treatment, mortality is still high and there still is not a cure despite great improvements have been made in therapies. The current treatment regimens for cancer have shown limited survival benefits when used for most advanced stage cancers, because these treatments primarily target tumor bulk but not cancer stem cells [1,2]. Indeed, conventional cancer therapies target neoplastic cells that are largely fast-growing, suggesting that cancer stem cells may survive due to their high resistance to drugs and slower proliferation rate [3]. All the traditional cancer therapies including surgery, hormonal therapy, anti-angiogenesis therapy, and immunotherapy show a lack of efficacy in terms of long-term outcome because of their failure to target cancer stem cells and toxicity due to non-specific effects on normal cells. In this review, we will focus on the following aspects: 1, Identification of cancer stem cells and therapies that were developed to target them. In recent years, some molecules (such as CD133, CD44, ABCG2, ALDH) have been defined as the biomarkers of some kind of cancer stem cells, and the aberrant signal pathways (such as Wnt, Notch and Hedgehog signal pathway) have also been suggested as another feature of cancer stem cells. Therapeutics that based on those characters have been developed and some are on clinical trials now. 2, we also discussed the natural compounds that own the ability to target cancer stem cells, the mesenchymal stem cell-mediated gene therapy, to induce cancer stem cell differentiation and some other therapies. Current research is helping us to understand cancer stem cells and in turn this will help to develop novel therapies to eliminate cancer and the initiating cancer stem cell.
Cancer stem cells are cancer cells that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. It is often considered to be associated with chemoresistance and radio-resistance that lead to the failure of traditional therapy [4]. There appear to be several sources from which cancer stem cells may arise. They may arise from normal ASCs (adipose-derived stromal cells), from more restricted progenitor cells or even from differentiated cells [5]. Normal stem cells are more likely to be the targets of mutants and leading to the formation of CSCs for they already possess active self-renewal pathways. It is also possible for progenitors and other differentiated cells to give rise to CSCs, though they would have to acquire more genetic mutations, especially in self-renewal genes. However, it has been hypotheses that CSCs arising from normal stem cells are more aggressive than those from progenitor cells, though this remains to be proven [6]. In cancer research experiments, tumor cells are sometimes injected into an experimental animal to establish a tumor. The efficient tumor formation requires thousands or tens of thousands of cells to be introduced, however, only a small fraction of the injected cells, the CSCs, have the potential to generate a tumor. In human acute myeloid leukemia the frequency of these cells is less than 1 in 10,000. The first CSC was identified in human acute myeloid leukemia (AML), showed that a rare malignant cell with the ability to repopulate the entire original disease over several transplantations, implying self-renewal and capacity to differentiate, was only found within the immature CD34+CD38-, but not the CD34+CD38+ subpopulation [7]. After that, cancer stem cells were found in some solid tumors subsequently. The first solid CSCs were identified in breast tumors in 2003 [8], and then CSCs were isolated from brain [9], colon [10], melanoma [11], pancreatic [12], prostate [13], ovarian [14], lung [15] and gastric [16] cancers. The emerging picture on CSCs is creating significant excitement and interest in the cancer field. It is believe that the targeting of CSCs offers important and revolutionary advances in the targeting of cancer. Eradicating cancer stem cells, the root of cancer origin and recurrence, has thought as a promising approach to improve cancer survival or even to cure cancer. In the research of killing cancer stem cells, many possible ways were developed to achieve this objective, including molecular targeted therapy, target molecular signaling pathways, natural compounds and their potent to target CSCs, the use of mesenchymal stem cells, and differentiation therapy. Though great progresses have been made in recent year, the accurate mechanism of cancer stem cell is still not clear and the really effective therapy is still not found. Here, we will discuss the new therapeutic approaches to cancer based on the existence of the cancer stem cells.
Cancer stem cells have been identified in a growing number of hematopoietic cancer and solid tumors and are typically recognized by virtue of the expression of cell surface markers. These cells have been isolated from the bulk-tumor population by the expression pattern of cell surface proteins (e.g., CD24, CD44, CD133) and cellular activities, such as the efflux of Hoechst dye or aldehyde dehydrogenase activity by flow cytometry and/or fluorescence activated cell sorting (FACS). The identification of markers that allow the prospective isolation of CSCs from whole tumor tissues will lead to the understanding of important biological properties of CSCs and provide the possibility to target them.
CD133 is a glycosylated, 120KD protein with five transmembrane domains and two large extracellular loops. CD133+ phenotype was first used to identify and isolate brain tumor stem cells in malignant tumors and now it has recently been used to define the CSC populations in lung, pancreati
c, liver, prostate, gastric, colorectal, and head and neck cancers. The expression of genes known to play important roles in the maintenance of cancer stem cells have been investigated in putative CD133+ CSC populations of multiple tissues. These CD133+ cells undergo multi-lineage differentiation to neurons, astrocytes, and oligodendrocytes in vitro, and can recapitulate the original tumor phenotype in vivo, unlike the CD133. Some genes associated with cancer stem cell like Nestin, BMI1, Olig2, and Nanog are also found upregulated in CD133+ populations of brain, lung, liver and prostate cancers [17-20]. CSCs is often associated with resistance to traditional chemotherapies, CD133+ cells have had increased survival in vitro and have been enriched in vivo after treatment with cisplatin, etoposide, doxorubicin, and paclitaxel, as the expression of genes known to be markers of stemness, ABC transporters and the DNA repair pathway [21,22].
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Frequently Asked Questions [FAQs] – Stem Cell Therapy New …
Posted: October 27, 2014 at 3:56 pm
Are there any ethical issues with Adult Stem Cells?
No, adult stem cells are not embryos. They dont have the potential to develop into a new human being. They reside in the bone marrow and fat and they exist in large quantities. Learn More
Consult with your physician if you have any type of joint pain or if you suffer from any degenerative disease. Stem Cell Therapy enables the patients body to use its own stem cells to heal and repair. Learn More
It is a very safe procedure. After a complete medical evaluation, our specialists will determine if you are a candidate for this treatment. Some patients may experience pain and soreness during the post-operative period. Because autologous blood and fat is used, there are minimal chances of allergic reactions. Learn More
Healing, repair and regeneration of injured or damaged tissue. It can regenerate tissues that are injured in meniscal tears, ligament tears, rotator cuff tear, tennis elbow and in degenerative diseases like arthritis and osteoarthritis. It decreases pain at the level of the injury and improves performance. The procedure is done in an office setting, under local anesthesia. This eliminates the risks associated with surgery or anesthesia. Learn More
Both types, adipose and bone marrow stem cells belong to a type of adult stem cell known as Mesenchymal Stem Cells. Adipose stem cells are collected via a mini liposuction procedure and bone marrow cells are aspirated from the hipbone. Bone marrow stem cells have a superior ability to repair and differentiate into ligaments, cartilage and bone. On the other hand, adipose stem cells have far regenerative properties to make new blood vessels, a process that is essential for oxygen and nutrient delivery to the tissues. Learn More
At AALMA we know that the success of any treatment relies on having a reliable delivery system. We use a very simple injection in and out method to deliver the stem cells and our injections are all done under fluoroscopy (x-ray) to visualize the site of injury and provide an accurate and effective treatment. Learn More
PRP is blood plasma that has a high autologous concentration of a group of cells called platelets. This cells release growth factors and other proteins that promote wound healing in bone and soft tissue. When we inject PRP, the high concentration of platelets, delivers powerful doses of growth factors that accelerate and enhance tissue repair and healing. These growth factors also attract Stem Cells to the site of injury. When injecting PRP, more than one injection is recommended to maximize results. Learn More
PRP is obtained with a simple and safe blood draw. Special collection tubes are used and about 16 cc of blood is obtained. The blood is centrifuged with special equipment until PRP is obtained. After this process the PRP is ready for injection or to be mixed with fat for aesthetic enhancement. Learn More
We encourage patients to undergo a simple detox before the treatment to prepare the body to be better conditioned to receive the stem cells. Patients should cease cigarette smoking and alcohol at least one week before the treatment. We recommend our IV Vitamin Therapy, which not only cleanses our system from toxins, but also at the same time, infuses vitamins and minerals in our bloodstream. These vitamins are required by some cells to carry out important functions. Having a good balance of these vitamins in our cells will enhance the effect of the treatment. Learn More
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Sarah heads to Russia in latest battle in war on MS
Posted: October 5, 2014 at 8:55 am
SARAH Woolford is not the sort of person to take a diagnosis of multiple sclerosis lying down.
Since being diagnosed in 2012, she has been researching its causes and the latest in MS medical research.
She has booked herself in to a Russian hospital next September to have a process called hematopoietic stem cell transplant (HSCT), which she hopes will stop the progress of the disease.
"I have a lot of life to live. I want to get to a good, ripe old age," she said.
The Casino mum says she has "good days and bad days" and at the moment is able to work three days a week as a teacher.
The process, which is only in trial stage in Australia, involves removing and storing stem cells from the patient before an extensive round of chemotherapy.
The stem cells are then transplanted back into the body to "re-boot the immune system". The process takes 30 to 35 days, including seven to 10 days in isolation when the immune system is at its lowest. Follow-up care is available in Brisbane.
The process is available in several countries but Sarah said Russia was the most affordable.
"This is something that is proven (to work); it's not new age," she said.
Sarah said it would cost $45,000 plus airfares to get the transplant done in Russia and she was already well under way with fundraising.
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