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Category Archives: Stem Cells
UF working to grow transplant kidneys from stem cells
Posted: January 25, 2014 at 11:50 pm
Dr. Edward Ross, with the University of Florida College of Medicine's Division of Nephrology, Hypertension and Renal Transplantation, talks about his research Thursday, January 16, 2014. Ross and his team are using pig kidneys as a scaffold or blueprint to someday recreate a human kidney.
In the ground-floor labyrinth that connects UF Health Shands Hospital to the UF health sciences campus, a handful of scientists are super excited about research that one day could mean the end of long waiting lines for kidney transplant patients.
The promise lies in a soft sponge-like structure that is about the size of a bar of soap and is considered a "scaffold" for building healthy human kidneys.
The soap-sized structure is a baby pig's kidney, drained of its blood and cells. Over the course of three days, chemicals strip the kidney of swine cells so it can be injected with human stem cells.
The idea of using stem cells to grow new organs is not new. Scientists have been plugging away at it for two decades, said Dr. Edward Ross, a nephrologist and professor of medicine at UF Health.
"The dream of taking patients' stem cells and growing an organ never came to fruition," Ross said. "Short of growing the organ de novo is (the idea) to somehow nudge the cells along to some sort of biological scaffold from a creature."
Pigs' kidneys are similar to those of humans in size and basic anatomy, so scientists have been studying the concept of using the pig's kidney as a scaffold. They also have experimented with rabbits and rats.
Scientists also have successfully grown human stem cells with other, "easier" organs such as the bladder and trachea, Ross said.
"(The kidney) is one of the most difficult because of the complexity of the organ," he said.
The scaffold is not, however, just an inert skeleton. It contains proteins with chemical signals that guide human stem cells once they are implanted, or "seeded," inside the scaffold. The kidney contains 30 different cell types, so the stem cells can differentiate into these types once inside the scaffold.
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UF working to grow transplant kidneys from stem cells
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Stem Cells Help Cerebral Palsy! Sophia's Story – Video
Posted: January 24, 2014 at 4:45 pm
Stem Cells Help Cerebral Palsy! Sophia #39;s Story
Meet Sophia. She came to Dr. Steenblock for stem cell therapy to help her Cerebral Palsy. Amazingly, the patient had great results after only one stem cell t...
By: David Steenblock
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Stem Cells Help Cerebral Palsy! Sophia's Story - Video
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Tracing unique cells with mathematics
Posted: January 24, 2014 at 4:45 pm
Jan. 23, 2014 Stem cells can turn into heart cells, skin cells can mutate to cancer cells; even cells of the same tissue type exhibit small heterogeneities. Scientists use single-cell analyses to investigate these heterogeneities. But the method is still laborious and considerable inaccuracies conceal smaller effects. Scientists at the Helmholtz Zentrum Muenchen, at the Technische Unitversitaet Muenchen and the University of Virginia (USA) have now found a way to simplify and improve the analysis by mathematical methods.
Each cell in our body is unique. Even cells of the same tissue type that look identical under the microscope differ slightly from each other. To understand how a heart cell can develop from a stem cell, why one beta-cell produces insulin and the other does not, or why a normal tissue cell suddenly mutates to a cancer cell, scientists have been targeting the activities of ribonucleic acid, RNA.
Proteins are constantly being assembled and disassembled in the cell. RNA molecules read blueprints for proteins from the DNA and initiate their production. In the last few years scientists around the world have developed sequencing methods that are capable of detecting all active RNA molecules within a single cell at a certain time.
At the end of December 2013 the journal Nature Methods declared single-cell sequencing the "Method of the Year." However, analysis of individual cells is extremely complex, and the handling of the cells generates errors and inaccuracies. Smaller differences in gene regulation can be overwhelmed by the statistical "noise."
Scientists led by Professor Fabian Theis, Chair of Mathematical modeling of biological systems at the Technische Universitaet Muenchen and director of the Institute of Computational Biology at the Helmholtz Zentrum Muenchen, have now found a way to considerably improve single-cell analysis by applying methods of mathematical statistics.
Instead of just one cell, they took 16-80 samples with ten cells each. "A sample of ten cells is much easier to handle," says Professor Theis. "With ten times the amount of cell material, the influences of ambient conditions can be markedly suppressed." However, cells with different properties are then distributed randomly on the samples. Therefore Theis's collaborator Christiane Fuchs developed statistical methods to still identify the single-cell properties in the mixture of signals.
On the basis of known biological data, Theis and Fuchs modeled the distribution for the case of genes that exhibit two well-defined regulatory states. Together with biologists Kevin Janes and Sameer Bajikar at the University of Virginia in Charlottesville (USA), they were able to prove experimentally that with the help of statistical methods samples containing ten cells deliver results of higher accuracy than can be achieved through analysis of the same number of single cell samples.
In many cases, several gene actions are triggered by the same factor. Even in such cases, the statistical method can be applied successfully. Fluorescent markers indicate the gene activities. The result is a mosaic, which again can be checked to spot whether different cells respond differently to the factor.
The method is so sensitive that it even shows one deviation in 40 otherwise identical cells. The fact that this difference actually is an effect and not a random outlier could be proven experimentally.
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Tracing unique cells with mathematics
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Cedars-Sinai clinical trial studies vaccine targeting cancer stem cells in brain cancers
Posted: January 24, 2014 at 4:45 pm
PUBLIC RELEASE DATE:
24-Jan-2014
Contact: Sandy Van sandy@prpacific.com 808-526-1708 Cedars-Sinai Medical Center
LOS ANGELES (Jan. 24, 2014) An early-phase clinical trial of an experimental vaccine that targets cancer stem cells in patients with recurrent glioblastoma multiforme, the most common and aggressive malignant brain tumor, has been launched by researchers at Cedars-Sinai's Department of Neurosurgery, Johnnie L. Cochran, Jr. Brain Tumor Center and Department of Neurology.
Like normal stem cells, cancer stem cells have the ability to self-renew and generate new cells, but instead of producing healthy cells, they create cancer cells. In theory, if the cancer stem cells can be destroyed, a tumor may not be able to sustain itself, but if the cancer originators are not removed or destroyed, a tumor will continue to return despite the use of existing cancer-killing therapies.
The Phase I study, which will enroll about 45 patients and last two years, evaluates safety and dosing of a vaccine created individually for each participant and designed to boost the immune system's natural ability to protect the body against foreign invaders called antigens. The drug targets a protein, CD133, found on cancer stem cells of some brain tumors and other cancers.
Immune system cells called dendritic cells will be derived from each patient's blood, combined with commercially prepared glioblastoma proteins and grown in the laboratory before being injected under the skin as a vaccine weekly for four weeks and then once every two months, according to Jeremy Rudnick, MD, neuro-oncologist in the Cedars-Sinai Department of Neurosurgery and Department of Neurology, the study's principal investigator.
Dendritic cells are the immune system's most powerful antigen-presenting cells those responsible for helping the immune system recognize invaders. By being loaded with specific protein fragments of CD133, the dendritic cells become "trained" to recognize the antigen as a target and stimulate an immune response when they come in contact.
The cancer stem cell study is the latest evolution in Cedars-Sinai's history of dendritic cell vaccine research, which was introduced experimentally in patient trials in 1998.
Cedars-Sinai's brain cancer stem cell study is open to patients whose glioblastoma multiforme has returned following surgical removal. Potential participants will be screened for eligibility requirements and undergo evaluations and medical tests at regular intervals. The vaccine and study-related tests and follow-up care will be provided at no cost to patients. For more information, call 1-800-CEDARS-1 or contact Cherry Sanchez by phone at 310-423-8100 or email cherry.sanchez@cshs.org.
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Cedars-Sinai clinical trial studies vaccine targeting cancer stem cells in brain cancers
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Stem cells could offer alternative treatment for patients with resistant tuberculosis
Posted: January 23, 2014 at 9:50 am
A team of international researchers has turned to stem cells in a quest to find an a more effective treatment for patients with drug-resistant tuberculosis (TB). The new method being investigated involves using the patients own bone marrow mesenchymal stromal cells (MSCs) to boost immune response and heal damaged tissue.
Multi-drug resistant TB effects around 450,000 in Eastern Europe, Asia, and South Africa according to the World Health Organization, and conventional treatments have a low rate of success.
Currently in its preliminary stages, the study is designed to investigate the possibility that MSCs can help organs to regulate themselves and repair damaged or traumatized tissues. Specifically in this case, the stem cells migrate to the lung with TB bacteria inflammation and improve the immune response to help the body get rid of the bacteria.
Between September 2009 and June 2011, the study looked at 30 patients from a specialist center in Minsk, Belarus, whose age varied from 21 to 65 years old, and who were resistant to TB drugs. They chose Belarus because of the high rate of resistant tuberculosis (76 percent) among treated patients in that region. They also observed 30 patients who met the inclusion criteria and who opted not to have MSC therapy.
Besides giving patients the anti-TB antibiotics, the researchers collected cells from their own bone marrow, cultured them and introduced them back into the patient within four weeks of the start of the anti-TB drug treatment. Eighteen months later, the rate of cure for patients who received MSC therapy was more than three times higher compared with those who didnt get treated with the cells.
MSC therapy produced a few side effects, which the researchers considered mild. Fourteen patients had high cholesterol, 11 patients suffered from nausea while 10 others had lymphopenia (low level of lymphocytes in the blood) or diarrhoea.
The researchers noted MSC cells harvested from TB patients did not present any aberrant features in comparison with those extracted from healthy donors. Neither did the anti-TB drugs seem to have a negative impact on the harvest. Concerns over the risk of suppressing an immune response, leading to the worsening of tuberculosis, did not materialize. However, they highlight that future studies would need to assess whether certain anti-M tuberculosis drug combinations or concomitant M. tuberculosis infection (a type of TB infection) could have an impact.
The results of this novel and exciting study show that the current challenges and difficulties of treating multi-drug resistant TB are not insurmountable, and they bring a unique opportunity with a fresh solution to treat hundreds of thousands of people who die unnecessarily of drug-resistant TB," says co-author Professor Alimuddin Zumla. "Further evaluation in phase 2 trials is now urgently required to ascertain efficacy and further safety in different geographical regions such as South Africa where multi-drug resistant and extensively-drug resistant TB are rife.
Details of the study are published in The Lancet Respiratory Medicine.
Source: UCL
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Insulin-producing beta cells from stem cells: Scientists decipher early molecular mechanisms of differentiation
Posted: January 23, 2014 at 9:50 am
2 hours ago Endodermal cells, they form organs such as lung, liver and pancreas. Credit: IDR, Helmholtz Zentrum Mnchen
The Wnt/-catenin signaling pathway and microRNA 335 are instrumental in helping form differentiated progenitor cells from stem cells. These are organized in germ layers and are thus the origin of different tissue types, including the pancreas and its insulin-producing beta cells. With these findings, Helmholtz Zentrum Mnchen scientists have discovered key molecular functions of stem cell differentiation which could be used for beta cell replacement therapy in diabetes. The results of the two studies were published in the renowned journal Development.
The findings of the scientists of the Institute of Diabetes and Regeneration Research (IDR) at Helmholtz Zentrum Mnchen (HMGU) provide new insights into the molecular regulation of stem cell differentiation. These results reveal important target structures for regenerative therapy approaches to chronic diseases such as diabetes.
During embryonic development, organ-specific cell types are formed from pluripotent stem cells, which can differentiate into all cell types of the human body. The pluripotent cells of the embryo organize themselves at an early stage in germ layers: the endoderm, mesoderm and ectoderm. From these three cell populations different functional tissue cells arise, such as skin cells, muscle cells, and specific organ cells.
Various signaling pathways are important for this germ layer organization, including the Wnt/-catenin signaling pathway. The cells of the pancreas, such as the beta cells, originate from the endoderm, the germ layer from which the gastrointestinal tract, the liver and the lungs also arise. Professor Heiko Lickert, director of the IDR, in collaboration with Professor Gunnar Schotta of LMU Mnchen, showed that the Wnt/-catenin signaling pathway regulates Sox17, which in turn regulates molecular programs that assign pluripotent cells to the endoderm, thus inducing an initial differentiation of the stem cells.
In another project Professor Lickert and his colleague Professor Fabian Theis, director of the Institute of Computational Biology (ICB) at Helmholtz Zentrum Mnchen, discovered an additional mechanism that influences the progenitor cells. miRNA-335, a messenger nucleic acid, regulates the endodermal transcription factors Sox17 and Foxa2 and is essential for the differentiation of cells within this germ layer and their demarcation from the adjacent mesoderm. The concentrations of the transcription factors determine here whether these cells develop into lung, liver or pancreas cells. To achieve these results, the scientists combined their expertise in experimental research with mathematical modeling.
"Our findings represent two key processes of stem cell differentiation," said Lickert. "With an improved understanding of cell formation we can succeed in generating functional specialized cells from stem cells. These could be used for a variety of therapeutic approaches. In diabetes, we may be able to replace the defective beta cells, but regenerative medicine also offers new therapeutic options for other organ defects and diseases."
Diabetes is characterized by a dysfunction of the insulin-producing beta cells of the pancreas. Regenerative treatment approaches aim to renew or replace these cells. An EU-funded research project ('HumEn'), in which Lickert and his team are participating, shall provide further insights in the field of beta-cell replacement therapy.
The aim of research at Helmholtz Zentrum Mnchen, a partner in the German Center for Diabetes Research (DZD), is to develop new approaches for the diagnosis, treatment and prevention of major common diseases such as diabetes mellitus.
Explore further: Stem cells on the road to specialization
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Insulin-producing beta cells from stem cells: Scientists decipher early molecular mechanisms of differentiation
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FASEB announces 2014 Science Research Conference: Skeletal Muscle Satellite and Stem Cells
Posted: January 23, 2014 at 9:50 am
PUBLIC RELEASE DATE:
22-Jan-2014
Contact: Robin Crawford src@faseb.org 301-634-7010 Federation of American Societies for Experimental Biology
Bethesda, MD This 2014 FASEB Science Research Conference focuses on recent advances in our understanding of the regulatory mechanisms controlling normal and abnormal functions of muscle-resident stem cells in regeneration, muscle homeostasis, hypertrophy, aging and muscle degenerative disease.
Eight plenary sessions and three dedicated poster sessions will encompass the following major themes: transcriptional and posttranscriptional regulation of gene expression in stem cells, satellite cell heterogeneity and potential, stem cell signaling and environmental interactions, satellite cell quiescence, activation and renewal, non-satellite stem cells, satellite cell proliferation, commitment and differentiation, muscle stem cells in growth and hypertrophy, and muscle stem cells in aging, disease and therapeutics.
This FASEB Conference increasingly attracts investigators in related fields who are interested in the rapid advances in muscle stem cell research, and interdisciplinary interactions are an important feature of this meeting. Collectively, this conference, which represents the only international conference that focuses exclusively on muscle satellite and stem cell populations, provides a venue to present cutting edge research, foster discussions, and promote collaborative interactions, with the goal of advancing a fundamental understanding of muscle-resident stem cells, and ultimately, translating this knowledge to the clinic.
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FASEB has announced a total of 35 Science Research Conferences (SRC) in 2014. Registration opens January 17, 2014. For more information about an SRC, view preliminary programs, or find a listing of all our 2014 SRCs, please visit http://www.faseb.org/SRC.
Since 1982, FASEB SRC has offered a continuing series of inter-disciplinary exchanges that are recognized as a valuable complement to the highly successful society meetings. Divided into small groups, scientists from around the world meet intimately and without distractions to explore new approaches to those research areas undergoing rapid scientific changes.
In efforts to expand the SRC series, potential organizers are encouraged to contact SRC staff at SRC@faseb.org. Proposal guidelines can be found at http://www.faseb.org/SRC.
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Study examines stem cell role in breast cancer care
Posted: January 23, 2014 at 9:50 am
Researchers at the Universitys Comprehensive Cancer Center, in collaboration with an international cohort, have developed means of identifying two states of breast cancer stem cells, giving them new clues as to how to treat patients with cancer.
By distinguishing the different states, they hope to find more targeted and effective treatments for the disease, which kills over 40,000 people each year in the U.S., according to the American Cancer Society.
What we found is that the stem cells actually are like chameleons that is they can exist in two different states, said Max S. Wicha, M.D., professor of Oncology and director of the University of Michigan Comprehensive Cancer Center.
In breast cancer, a small fraction of cells act as seeds of the tumor, Wicha said. Cells in this state, known as epithelial-mesenchymal transition, are dormant but can spread to other organs in the body.
The process of these cells spreading is called metastasis, and studying this process has been a key component of the research findings. The previous dearth of research on the dormant cells within the process of metastasis has posed a challenge to researchers trying to find new treatment options.
As a matter of fact, in breast cancer, we sometimes have women that go out ten or 15 years and we think are cured, and then the cancer, it turns out, was hiding in the bone, Wicha said.
Moreover, the new findings show that these exact same cells have the capacity to switch states, causing them to not only look different under the microscope, but also turn on different genes in the cell.
When the cells enter the mesenchymal-epithelial transition state, they can no longer invade tissues but they can grow and reproduce into malignant tumors.
The tumor microenvironment enables these cells to flip back and forth between the EMT and MET-states, researchers said. While the cells plasticity seems to be the reason that they are able to flip between two states, the reason for the cells ability to switch states at any given time is unclear.
Were very interested in studying whether things like stress that may change some of the proteins or hormones in your body may actually cause the cells to change their state and come out of dormancy, Wicha said.
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City of Hope's Dr. Margarita Gutova talks about using neural stem cells to treat brain tumors – Video
Posted: January 22, 2014 at 9:54 am
City of Hope #39;s Dr. Margarita Gutova talks about using neural stem cells to treat brain tumors
City of Hope scientist Margarita Gutova, M.D., talks about her research using neural stem cells to help target and treat medulloblastoma, the most common for...
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Pluristem stem cell trial to treat muscle injury meets main goal
Posted: January 22, 2014 at 9:54 am
Pluristem Therapeutics Inc said results from its early/mid-stage clinical trial indicated its placenta-derived stem cells for the treatment of muscle injury were safe and provided evidence the cells might be effective in treating orthopedic injuries.
"Patients treated with PLX-PAD had a greater improved change of maximal voluntary muscle contraction force than the placebo group," Israel-based Pluristem said in a statement on Tuesday.
The trial was conducted at the Orthopedic Clinic of the Charite University Medical School under the auspices of the Paul-Ehrlich-Institute, Germany's health authority.
"This was a very important study not only for Pluristem but for the cell therapy industry in general," Pluristem chief executive Zami Aberman said. "Based on these results, we intend to move forward with implementing our strategy towards using PLX cells in orthopedic indications and muscle trauma."
The injured muscle studied was the gluteus medius muscle in the buttock. Total hip replacement surgery via the standard transgluteal approach necessitates injury of the gluteus medius muscle, and post-operative healing is crucial for joint stability and function.
"The study showed that PLX-PAD cells were safe and well tolerated," the statement said.
The primary efficacy endpoint of the study was the change in maximal voluntary isometric contraction force of the gluteal muscle six months after surgery.
Efficacy was shown in two groups treated with the cells, with one group receiving a 150 million cell dose displaying a 500 percent improvement over the placebo group. Patients treated with a 300 million cell dose showed a 300 percent improvement over the placebo.
An analysis of the gluteal muscle indicated an increase in muscle volume in those patients treated with PLX-PAD cells versus the placebo group.
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