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Category Archives: Stem Cell Research

Existing Drug Found to be Effective at Killing Cancer Stem Cells – Technology Networks

Posted: June 26, 2017 at 10:48 am

Researchers experiment with the Sam68 protein. Credit: McMaster University

A team of researchers at McMaster University has identified a unique feature of cancer stem cells that can be exploited to kill the deadly cells thought to be the reason that cancer comes back after therapy. Understanding this feature will be useful for delivering more targeted cancer therapeutics to the right patients.

The study, published today in the scientific journal Cell Chemical Biology, reveals that an existing set of drugs is effective in killing cancer stem cells and explains how this led the team to uncovering important details about how these cells are working in human tumors.

“The drugs helped us to understand the biology,” said Mick Bhatia, principal investigator of the study and scientific director of the McMaster Stem Cell and Cancer Research Institute. “We’ve worked backwards, employing a series of drugs used in the clinic to understand a new way that cancer stem cells can be killed.”

The researchers found that a particular protein, called Sam68, is an important actor in cancer stem cells, and that this protein allows existing drugs to work on cancer cells, causing them to die.

Bhatia hopes that this information can be used to deliver targeted therapies to the patients who would benefit from them, while sparing others from unhelpful treatments. He believes that treatment of blood cancers like leukemia and other cancers such as prostate, colon and renal will follow the example set in breast cancer, where patients receive treatments tailored to their specific form of the disease.

“In the case of breast cancer, other researchers have found new ways to make existing drugs more effective by only giving them to people who were likely to benefit based on their specific traits and using drugs that target these traits,” Bhatia said.

He said while developing a new drug takes an average of about 15 years and comes with a price tag in the hundreds of millions, defining the role of existing drugs to use them better in patients will help to accelerate the process of bringing the right drugs to the right people.

Reference

Mickie Bhatia et al. Sam68 Allows Selective Targeting of Human Cancer Stem Cells. Cell Chemical Biology, June 2017 DOI: 10.1016/j.chembiol.2017.05.026

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Large-scale production of living brain cells enables entirely new research – Medical Xpress

Posted: at 10:48 am

June 26, 2017

Important pieces of the puzzle to understand what drives diseases such as Alzheimer’s and Parkinson’s are still missing today. One crucial obstacle for researchers is that it is impossible to examine a living brain cell in someone who is affected by the disease. With the help of a new method for cell conversion, researchers at Lund University in Sweden have found a way to produce diseased, aging brain cells on a large scale in a cell culture dish.

After performing a biopsy on the patient, the skin cells are transformed into brain cells that effectively imitate the disease and the age of the patient. The fact that the cells can now be produced in large quantities enables researchers to carry out a series of experiments that were previously not possible.

A few years ago, Malin Parmar’s research team was one of the first in the world to convert human skin cells directly into brain cells without passing the stem cell state. The discovery shocked the researchers and was perceived as almost impossible. The team is now approaching a point where the discovery is about to bear fruit on a wide scale. By following a new method that involves slightly changing the genetic code that triggers cell conversion, the researchers were able to multiply the production of disease-specific brain cells.

“Primarily, we inhibited a protein, REST, involved in establishing identity in cells that are not nerve cells. After limiting this protein’s impact in the cells during the conversion process, we’ve seen completely different results. Since then, we’ve been playing around with changing the dosage of the other components in the previous method, which also proved effective. Overall, the efficiency is remarkable. We can now generate almost unlimited amounts of neurons from one skin biopsy”, says Malin Parmar, professor of developmental and regenerative neurobiology at Lund University.

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The increase in production will have far-reaching effects. The new volumes enable research projects that were simply not viable before. Among other things, it opens up research areas linked to new drug testing, the establishment of more accurate disease models and the development of diagnostics to detect the diseases at an earlier stage.

The new cells are not only able to imitate the disease but also the patient’s age. By studying the cell in the culture dish, the researchers can now monitor the mechanisms of the disease in an “old” brain cell over time. Neurodegenerative diseases are commonly referred to as “aging brain diseases” and in order to understand them, we must better appreciate how the age specifically affects the course of the disease. The Lund researchers’ discovery can hopefully contribute a crucial piece to the puzzle with regard to the connection between the onset of disease and cell aging, something which previous research based on animal experiments and stem cells has failed to provide.

“This takes us one step closer to reality, as we can now look inside the human neurons and see what goes on inside the cell in these diseases. If all goes well, this could fundamentally change the field of research, as it helps us better understand the real mechanisms of the disease. We believe that many laboratories around the world would like to start testing on these cells to get closer to the diseases”, says Johan Jakobsson, leader of the molecular neurogenetics research group at Lund University.

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Clear View on Stem Cell Development – Technology Networks

Posted: June 24, 2017 at 8:44 am

Today, tracking the development of individual cells and spotting the associated factors under the microscope is nothing unusual. However, impairments like shadows or changes in the background complicate the interpretation of data. Now, researchers at the Technical University of Munich (TUM) and the Helmholtz Zentrum Mnchen have developed a software that corrects images to make hidden development steps visible.

When stem cells develop into specialized cells, this happens in multiple steps. But which regulatory proteins are active during the decisive branching on the development path? Using so-called time-lapse microscopy, researchers can observe individual cells at very high time resolutions and, using fluorescent labelling, they can recognize precisely which of these proteins appear when in the cell.

Once a stem cell has been identified, it can be closely observed over several days using cell-tracking software. Yet, this surveillance work often turns out to be difficult. The imaging data is frequently marred by irregular brightness and faded backgrounds in the time-lapse, explains Dr. Carsten Marr, heading the workgroup Quantitative Single Cell Dynamics at the Institute of Computational Biology (ICB) of the Helmholtz Zentrum Mnchen. This makes it difficult or impossible to detect proteins that are decisive when a cell opts for a specific development direction, so-called transcription factors.

Algorithms that filter out these kinds of artefacts exist, but they require either specifically prepared reference images, many images per dataset or complex manual adjustments. Furthermore, none of the existing methods correct alterations in the background over time, which hamper the quantification of individual cells.

Algorithm eliminates background changes Now, Dr. Tingying Peng, member of Dr. Carsten Marrs group at the Helmholtz Zentrum Mnchen and Professor Nassir Navab, head of the Chair for Computer Aided Medical Procedures and Augmented Reality at TU Munich, present an algorithm that corrects these artefacts using only a few images per dataset.

The software is called BaSiC and is freely available. It is compatible with many image formats commonly used in bioimaging, including mosaics pieced together from numerous smaller images and used, for example, to render large tissue regions. Contrary to other programs, however, explains Dr. Peng, BaSiC can correct changes in the background of time-lapse videos. This makes it a valuable tool for stem cell researchers who want to detect the appearance of specific transcription factors early on. Bringing significant details to light How well the new image correction program improves the analysis of individual stem cell development steps the scientists demonstrated with time-lapse videos of blood stem cells. They recorded the videos to observe cells over a six-day time span. At a certain point during this observation period undifferentiated precursor cells choose between two possible tacks of development that lead to the formation of different mature blood cells.

In images corrected using BaSiC, the researchers could identify a substantial increase in the intensity of a specific transcription factor in one of the two cell lines, while the amount of his protein in the other cell line remained unchanged. Without the image correction, the difference was not ascertainable.

Using BaSiC, we were able to make important decision factors visible that would otherwise have been drowned out by noise, says Nassir Navab. The long-term goal of this research is to facilitate influencing the development of stem cells in a targeted manner, for example to cultivate new heart muscle cells for heat-attack patients. The novel possibilities for observation are bringing us a step closer to this goal.

The BaSiC image correction program resulted from a close collaboration between the Chair of Mathematical Modeling of Biological Systems and the Chair of Computer Aided Medical Procedures & Augmented Reality at the Technical University of Munich and the Institute of Computational Biology (ICB) of the Helmholtz Zentrum Mnchen. Also involved were the Department of Biochemistry and Biophysics at the University of California in San Francisco (USA), as well as the Department of Biosystems Science and Engineering (D-BSSSE) at ETH Zrich and the Chair of Computer Aided Medical Procedure at Johns Hopkins University in Baltimore (USA).

This article has been republished frommaterialsprovided by the Technical University of Munich. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:

Tingying Peng, Kurt Thorn, Timm Schroeder, Lichao Wang, Fabian J. Theis, Carsten Marr and Nassir Navab. BaSiC: A Tool for Background and Shading Correction of Optical Microscopy Images. Nature Communications 8, 14836 (2017) DOI: 10.1038/ncomms14836

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Clear View on Stem Cell Development – Technology Networks

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Stem cells: the future of medicine – Medical Xpress

Posted: at 8:44 am

June 23, 2017

Imagine being able to take cells from your skin, transform them into other types of cells, such as lung, brain, heart or muscle cells, and use those to cure your ailments, from diabetes to heart disease or macular degeneration. To realise this, however, challenges still remain, Professor Janet Rossant, a pioneer in the field, says.

All across the world, scientists have begun clinical trials to try and do just that, by making use of the incredible power and versatility of stem cells, which are special cells that can make endless copies of themselves and transform into every other type of cell.

While human embryos contain embryonic stem cells, which help them to develop, the use of those cells has been controversial. The scientists are using induced pluripotent stem cells instead, which are other cells that have been reprogrammed to behave like stem cells.

“There are still significant challenges that we need to overcome, but in the long run we might even be able to create organs from stem cells taken from patients. That would enable rejection-free transplants,” said Professor Janet Rossant, a pioneer in the field.

The mouse that changed everything

A speaker at the recent Commonwealth Science Conference 2017 held in Singapore and organised by Britain’s Royal Society and Singapore’s National Research Foundation, Prof Rossant gave an overview of stem cells’ origins, history, uses and potential.

Now a senior scientist at The Hospital for Sick Children (also known as Sick Kids) in Toronto, Canada, after a decade as its chief of research, she was the first scientist to demonstrate the full power of stem cells in mice.

In the early 1990s, scientists believed that stem cells could only become certain types of cells and carry out limited functions. Based on her own research and that of others, however, Prof Rossant believed that they were capable of far more.

Working with other scientists, she created an entire mouse out of stem cells in 1992, upending the conventional wisdom. “We went on to create many baby mice that were completely normal, and completely derived from stem cells grown in a petri dish,” she said.

“That was an amazing experiment, and it was instrumental in making people believe that human embryonic stem cells could have the full potential to make every cell type in the body,” she added.

When scientists learned how to remove stem cells from human embryos in 1998, however, controversy ensued. Many lobbied against the cells’ use in medical research and treatment due to the moral implications of destroying even unwanted embryos to gain the cells.

In Canada, Prof Rossant chaired the working group of the Canadian Institutes of Health Research on Stem Cell Research, establishing guidelines for the field. These guidelines helped to keep the field alive in Canada, and were influential well beyond the country’s borders.

In 2006, Japanese researchers succeeded in taking skin cells from adult mice and reprogramming them to behave like embryonic stem cells. These revolutionary, induced pluripotent stem (IPS) cells allowed scientists to sidestep the ongoing controversy.

The challenges in the way

While stem cells have been used for medical treatment in some cases bone marrow transplants, for example, are a form of stem cell therapy there are several challenges that need to be overcome before they can be used more widely to treat diseases and injuries.

“We need to get better at turning stem cells into the fully mature cells that you need for therapy. That’s going to take more work. Another issue is that of scale-up. If you’re going to treat a patient, you need to be able to grow millions of cells,” said Prof Rossant.

She added: “Safety is another concern. One of the most exciting things about pluripotent stem cells is that they can divide indefinitely in the culture dish. But that’s also one of the most scary things about them, because that’s also how cancer works.

“Furthermore, because we need to genetically manipulate cells to get IPS cells, it’s very hard to know whether we’ve got completely normal cells at the end of the day. These are all issues that need to be resolved.”

She noted that some scientists are working on making “failsafe” IPS cells, which have a built-in self-destruct option if they become dangerous. “Bringing stem cells into regenerative medicine is going to require interdisciplinary, international collaboration,” she said.

In the meantime, stem cells have been a boon to medical research, as scientists can use them to create an endless supply of different cells to study diseases and injuries, and test drugs. “That’s the biggest use of IPS cells right now,” Prof Rossant said.

Sick kids and how to help them

At SickKids, which is Canada’s largest paediatric research hospital, she has been using stem cells to study cystic fibrosis, a frequently fatal genetic disorder that causes mucus to build up and clog some organs such as the lungs. It affects primarily children and young adults.

SickKids discovered the CFTR gene that, when mutated, causes the disease. It was also the first to produce mature lung cells, from stem cells, that can be used to study the disease and test drugs against it.

Even better, Prof Rossant and her team were able to turn skin cells from cystic fibrosis patients into IPS cells and then into lung cells with the genetic mutation specific to each of them. This is critical to personalising treatment for each patient.

“Drugs for cystic fibrosis are extraordinarily expensive, and patients can have the same mutation and yet respond differently to the same drug,” Prof Rossant explained. “With our work, we can make sure that each patient gets the right drug at the right time.”

In 1998, Prof Rossant also discovered a new type of stem cell in mice, now called the trophoblast stem cell. These surround an embryo and attach it to the uterine wall, eventually becoming the placenta. She is using such cells to study placenta defects and pregnancy problems.

By using IPS cells to create heart cells and other cells, pharmaceutical companies can also test their new drugs’ effectiveness and uncover potential side effects, as well as develop personalised medicines.

“There are still huge amounts of opportunities in pluripotent stem cells,” said Prof Rossant, who has won numerous awards for her research, including the Companion of the Order of Canada and the 2016 Friesen International Prize in Health Research.

She is also president and scientific director of the Toronto-based Gairdner Foundation, which recognises outstanding biomedical research worldwide, and a professor at the University of Toronto’s molecular genetics, obstetrics and gynaecology departments.

“Meetings like the Commonwealth Science Conference are a fantastic opportunity for scientists to come together, learn about each other’s work and establish new relationships, which will help to push science forward, including in stem cell research,” she said.

She noted: “The world of science is becoming increasingly interdisciplinary, so this kind of meeting of minds across nations, cultures and scientific fields is really the way of the future.”

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Eva Feldman reflects on experience as director of Taubman Institute – The Michigan Daily

Posted: June 23, 2017 at 5:46 am

Eva Feldman has been at the forefront of the University of Michigans stem cell research for decades. Since receiving her M.D. and Ph.D. degrees from the University and, later, becoming director of research for the University Amyotrophic Lateral Sclerosis Clinic and director of the A. Alfred Taubman Medical Research Institute, Feldman has conducted her research with one thing in mind: finding a cure for ALS.

Though Feldman recently announced she will be stepping down from the latter position, her extensive research and numerous accomplishments as director of the Taubman Institute will not be forgotten by peers, mentees and most importantly her patients.

Stem cell research, though controversial, has always been a noteworthy point of scientific and medical innovation and development at the University despite pushback from human rights groups and government action.

Feldman herself has been conducting her research for years, starting first as a fellow at the University in 1987, then later joining as a faculty member, practicing clinical trials and speaking at events to stress the significance of stem cell research. She conducts research primarily on amyotrophic lateral sclerosis, commonly known as Lou Gehrig’s disease a neurodegenerative disease which the Centers for Disease Control and Prevention estimates 5,000 people in the U.S. are diagnosed with each year.

The creation of the Taubman Institute first stemmed from a unique friendship between Feldman and one of her early patients, A. Alfred Taubman. While Feldman was Taubmans physician, he became more and more interested in medical research and funded her work several times.

I said, you know Alfred, we need to do something bigger than just me, Feldman said.

With the help of then-University President Mary Sue Coleman and other administrators, the Taubman was founded in 2007, aiming to allow researchers to pursue all avenues of biomedical research at the University.

He was the worlds best patient, Feldman laughed, noting Taubman even had his own white lab coat when visiting her lab. Feldman recognized his willingness to learn about her research and help close a gap present at the University in terms of this work.

Starting with just four central physician scientists a decade ago, the institute has more than 200 working researchers today, and while it is centered around the study of neurodegenerative disease, cancer and cardiovascular disease, researchers also touch on a variety of other medical research areas.

Feldman, who has served as director of the institute since its inception and is a Russell N. DeJong Professor of Neurology, said her inspiration for her research stems from a desire to make positive and impactful discoveries in neurology and cancer care.

Our goal has always been to understand the pathogenesis of neurological disorders and create new therapies, Feldman said, recalling the impact that seeing one of her first patients had on her. This patient was a woman just a few years older than her at the time who had ALS.

Feldman has received a number of awards and authored countless academic articles regarding her work many of which have been acknowledged in medical news across the nation all motivated by the patients and diseases seen.

Starting to see patients when I was young made me realize that this is what I wanted to do, Feldman said.

The work of Feldman and her closest peers have also led scientists closer to a cure for ALS than ever. This isnt to say Feldman hasnt faced challenges, however namely, finances. The institute was born just prior to the 2008 recession, prompting researchers there to find new ways to gain access to local, pharmaceutical and national funding.

Theres certainly now, at the medical center, a much more robust infrastructure to help individuals with the novel ideas theyve created as Taubman scholars to bring them forth to the clinic, Feldman said. Thats one of the underlying tenants and one of the underlying visions of the institute, is to let a clinician scientist take that discovery and bring it into the clinic.

Aside from finances, gaining recognition within the University was a challenge at the beginning. Now, however, the institute has gained national recognition.

Max Wicha, director of the Forbes Institute for Cancer Discovery and one of the founding scholars of the Taubman, attributed much of the institutes success to Feldman and her dedication to medical treatment and innovation.

One characteristic above all is that shes amazingly caring and really wants to help other people and help their career and also to move science forward very unselfish, Wicha said.

Wicha admired the work of Feldman as a physician scientist, a challenging task he has experienced himself. Being pulled in two directions both conducting lab research and regularly seeing patients can be demanding, he said, but rewarding.

She saw the need, as I do, that physician scientists were critical, because dealing with patients, they really understand the disease processes, Wicha said.

Wicha said Feldmans emphasis on emerging physician scientists and scholars and team science has also led the Taubman Institute to become more multidisciplinary within the University.

However, Feldman said there is still work to be done, one reason she will continue to do research after she steps down from the position.

Feldman will be working to get her trial for stem cells approved by the FDA; in the meantime, shell always look back on the phenomenal work she got to be a part of as director of the Taubman.

I just had the last ten best years of my life, and its really exciting to pass the baton to someone who could have the next ten best years of their life, taking what weve established and then using their vision to grow it or to move it in different, innovative, novel directions, Feldman said.

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Clear view on stem cell development – Phys.org – Phys.Org

Posted: June 22, 2017 at 2:44 pm

June 21, 2017 The software BaSiC improves microscope images, e.g., the mosaic image of a mouse brain thin section (left without, right with BaSiC correction). BaSiC’s image correction is also a valuable tool for stem cell researchers who want to detect the appearance of specific transcription factors early on. Credit: Tingying Peng / TUM/HMGU

Today, tracking the development of individual cells and spotting the associated factors under the microscope is nothing unusual. However, impairments like shadows or changes in the background complicate the interpretation of data. Now, researchers at the Technical University of Munich (TUM) and the Helmholtz Zentrum Mnchen have developed a software that corrects images to make hitherto hidden development steps visible.

When stem cells develop into specialized cells, this happens in multiple steps. But which regulatory proteins are active during the decisive branching on the development path? Using so-called time-lapse microscopy, researchers can observe individual cells at very high time resolutions and, using fluorescent labelling, they can recognize precisely which of these proteins appear when in the cell.

Once a stem cell has been identified, it can be closely observed over several days using cell-tracking software. Yet, this “surveillance work” often turns out to be difficult. “The imaging data is frequently marred by irregular brightness and faded backgrounds in the time-lapse,” explains Dr. Carsten Marr, heading the workgroup Quantitative Single Cell Dynamics at the Institute of Computational Biology (ICB) of the Helmholtz Zentrum Mnchen. “This makes it difficult or impossible to detect proteins that are decisive when a cell opts for a specific development direction, so-called transcription factors.”

Algorithms that filter out these kinds of artefacts exist, but they require either specifically prepared reference images, many images per dataset or complex manual adjustments. Furthermore, none of the existing methods correct alterations in the background over time, which hamper the quantification of individual cells.

Algorithm eliminates background changes

Now, Dr. Tingying Peng, member of Dr. Carsten Marr’s group at the Helmholtz Zentrum Mnchen and Professor Nassir Navab, head of the Chair for Computer Aided Medical Procedures and Augmented Reality at TU Munich, present an algorithm that corrects these artefacts using only a few images per dataset.

The software is called “BaSiC” and is freely available. It is compatible with many image formats commonly used in bioimaging, including mosaics pieced together from numerous smaller images and used, for example, to render large tissue regions. “Contrary to other programs, however,” explains Dr. Peng, “BaSiC can correct changes in the background of time-lapse videos. This makes it a valuable tool for stem cell researchers who want to detect the appearance of specific transcription factors early on.”

Bringing significant details to light

How well the new image correction program improves the analysis of individual stem cell development steps the scientists demonstrated with time-lapse videos of blood stem cells. They recorded the videos to observe cells over a six-day time span. At a certain point during this observation period undifferentiated precursor cells choose between two possible tacks of development that lead to the formation of different mature blood cells.

In images corrected using BaSiC, the researchers could identify a substantial increase in the intensity of a specific transcription factor in one of the two cell lines, while the amount of his protein in the other cell line remained unchanged. Without the image correction, the difference was not ascertainable.

“Using BaSiC, we were able to make important decision factors visible that would otherwise have been drowned out by noise,” says Nassir Navab. “The long-term goal of this research is to facilitate influencing the development of stem cells in a targeted manner, for example to cultivate new heart muscle cells for heat-attack patients. The novel possibilities for observation are bringing us a step closer to this goal.”

Explore further: Deep learning predicts hematopoietic stem cell development

More information: Tingying Peng et al, A BaSiC tool for background and shading correction of optical microscopy images, Nature Communications (2017). DOI: 10.1038/ncomms14836

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Grape-based compounds kill colon cancer stem cells in mice – Penn State News

Posted: at 2:44 pm

UNIVERSITY PARK, Pa. Compounds from grapes may kill colon cancer stem cells both in a petri dish and in mice, according to a team of researchers.

The compounds resveratrol which are found in grape skins and seeds, could also eventually lead to treatments to help prevent colon cancer, said Jairam K.P. Vanamala, associate professor of food sciences, Penn State. Colorectal cancer is the second leading cause of cancer-related deaths in the U.S., according to the American Cancer Society.

“The combination of resveratrol and grape seed extract is very effective at killing colon cancer cells,” said Vanamala, who is also a faculty member at the Penn State Hershey Cancer Institute. “And what we’re learning is the combination of these compounds is not toxic to healthy cells.”

The researchers, who reported their findings in a recent issue of BMC Complementary and Alternative Medicine, suggest that the findings could pave the way for clinical testing of the compounds on human colon cancer, which is the second most common cancer in women and the third in men. If successful, the compounds could then be used in a pill to help prevent colon cancer and lessen the recurrence of the disease in colon cancer survivors.

“We are particularly interested in targeting stem cells because, according to cancer stem-cell theory, cancerous tumors are driven by cancer stem cells,” said Vanamala. “Cancer stem cells are capable of self-renewal, cellular differentiation and maintain their stem cell-like characteristics even after invasion and metastasis.”

When taken separately in low doses, resveratrol and grape seed extract are not as effective against cancer stem-cell suppression as when they are combined together, according to the researchers.

The combined effect of grape seed extract and resveratrol may offer clues as to why cultures with a plant-based diet tend to have lower colon cancer rates, said Vanamala. These diets may naturally be providing a shotgun approach to cancer prevention by using a wide variety of beneficial compounds to target multiple pathways that cancer stem cells use to survive.

Jairam Vanamala suggests eating a wide-variety of colorful vegetables and fruits may help treat chronic diseases such as colon cancer and type-2 diabetes.

“This also connects well with a plant-based diet that is structured so that the person is getting a little bit of different types of plants, of different parts of the plant and different colors of the plant,” said Vanamala. “This seems to be beneficial for not only promoting bacterial diversity, but also preventing chronic diseases and eliminating the colon cancer stem cells.”

If successful in human trials, the compounds could be taken in low doses using currently available supplements for grape seed extract and resveratrol, which are also found in wine.

However, he added that there is still more work to do to understand the mechanism behind the anti-cancer properties of the grape extract, as well as other colorful fruits and vegetables. Further research would be aimed at finding specific anti-cancer compounds and better understanding how those compounds work synergistically to create more effective colon-cancer prevention and treatment strategies.

For the animal study, the researchers separated 52 mice with colon cancer tumors into three groups, including a control group and groups that were fed either the grape compounds or sulindac, an anti-inflammatory drug, which was chosen because a previous study showed it significantly reduced the number of tumors in humans.

The incidence of tumors was suppressed in the mice consuming the grape compounds alone by 50 percent, similar to the rate in the group consuming the diet with sulindac.

Vanamala worked with Joshua D. Lambert and Ryan J. Eilas, both associate professors of food science; Lavanya Reddivari, assistant professor of plant science; Sridhar Radhakrishnan, a postdoctoral scholar and Venkata Charepalli, a doctoral student, all from Penn State; and Ramakrishna Vadde, a visiting scientist from India.

The United States Department of Agriculture supported this work.

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Grape compounds can kill colon cancer cells: Research – The Indian Express

Posted: June 21, 2017 at 7:41 am

By: IANS | New York | Published:June 21, 2017 4:48 pm The combination of resveratrol (found largely in grape skins) and grape seed extract is very effective at killing colon cancer cells.(Source: File photo)

Compounds found in grape skins and seeds can kill colon cancer cells and may eventually lead to treatments to help prevent the condition, say researchers including one of Indian origin.

The combination of resveratrol (found largely in grape skins) and grape seed extract is very effective at killing colon cancer cells, said Jairam K.P. Vanamala, Associate Professor of Food Sciences at Pennsylvania State University in the US.

And what were learning is the combination of these compounds is not toxic to healthy cells, Vanamala, who is also a faculty member at the Penn State Hershey Cancer Institute, said. The findings, published in the journal BMC Complementary and Alternative Medicine, could pave the way for clinical testing of the compounds in human colon cancer, which is the second most common cancer in women and the third in men.

If successful, the compounds could then be used in a pill to help prevent colon cancer and lessen the recurrence of the disease in colon cancer survivors. The researchers found that grape compounds can kill colon cancer stem cells both in a petri dish and in mice.

We are particularly interested in targeting stem cells because, according to cancer stem-cell theory, cancerous tumours are driven by cancer stem cells, said Vanamala.

For the animal study, the researchers separated 52 mice with colon cancer tumours into three groups, including a control group and groups that were fed either the grape compounds or sulindac, an anti-inflammatory drug, which was chosen because a previous study showed it significantly reduced the number of tumours in humans. The incidence of tumours was suppressed in the mice consuming the grape compounds alone by 50 per cent, similar to the rate in the group consuming the diet with sulindac.

When taken separately in low doses, resveratrol and grape seed extract are not as effective against cancer stem-cell suppression as when they are combined together, according to the researchers. If successful in human trials, the compounds could be taken in low doses using currently available supplements for grape seed extract and resveratrol, which are also found in wine, according to the researchers.

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He broke ground in stem-cell research. Now he’s running for Congress. – Washington Post

Posted: June 20, 2017 at 9:47 am

The small pack of scientists running for political office has grown by one.

Stem-cell researcher Hans Keirstead, 50, announced last week that he will try to unseat Californias Rep. Dana Rohrabacher (R). Keirstead, a Democrat with a PhD in neuroscience from the University of British Columbia, was a professor at the University of California at Irvinebefore launching and selling several biotech companies.

Rohrabacher, who represents the 48th District in Southern California, has been in Congress since 1988. Democrats there see 2018 asa vulnerable year for the incumbent. Although Republicans outnumber Democrats in thedistrict, Hillary Clinton swung it in the 2016 election. And Rohrabacher has come under scrutiny for his support of acloser relationship with Russia. In May, the chair of Orange County Democrats toldThe Washington Post that challengers were coming out the woodwork to oppose him. Five candidatesbesides Keirstead have declared they are running for the seat.

Keirstead emerged from academic and entrepreneurial fields. Hepioneered a technique to purify stem cells You cant go putting toenails into the spinal cord, he said and applied this method to spinal-cord injuries and diseases such ascancer and amyotrophic lateral sclerosis, or ALS. In 2014,he sold a stem-cell company in a deal reportedly worth more than $100 million. (He will not fundhis own campaign, he told the Los Angeles Times.) Keirstead has thesupportof314 Action, a nonprofit group that encourages scientists to seek public office.

The Post spoke by phone with the first-time candidate. The following is lightly edited for space and clarity.

TWP: Your opponent, who is a member of the House Science Committee, told Science magazine in 2012 that he loved science. How would you compare your approaches to science?

Keirstead:Im delighted that Dana Rohrabacher loves science. Thats fabulous. But Im also very convinced that he doesnt understand science. Theres a real big difference. If you love science, thats one thing. If you dont understand it, you cant effect change, and you make wrong decisions.

Dana Rohrabacher does not understand global warming. He actually attributed it to the flatulence of dinosaurs, in a serious manner, a while back. [Rohrabacher hassaid this wasa joketo make fun of scientists who study cow methane.]

His inaction and lack of understanding has tremendous detriment on the scientific community. Likewise is the funding to health care and how to fix the health-care system that [former president Barack] Obama put in place. That was not a perfect system by any means; its got problems.But it has also bettered our system. It needs to be worked with in order to further better our system.

TWP: Has your career in stem-cell research influenced your politics?

Keirstead:I was front and center in the national and international debate on stem cells. I was the first scientist in the world to have developed a treatment for spinal-cord injury using stem cells. The dramatic nature of the recovery we saw in rodents, going from paralyzed to walking, drew a great deal of attention and really put me at the center of this issue as it was just coming to light in the public forums.

I did a lot of advising of senators and congressmen all throughout those years and periodically since that time. . . . I was one of the key scientific advisers to Proposition 71 that turned into the $3 billion California Institute of Regenerative Medicine, a not-for-profit that distributes $300 million every year for regenerative medicine in a broad sense.

That was a very good example of how medical breakthroughs and discoveries and advancement are not at odds with economic development. You do not have to cut medical budgets to stimulate the economy. Any scientist and medical doctor will tell you: Give me some time, and I will generate a treatment. And most of the time they are right. What happens with that treatment is small companies are born, people stop dying, quality of life improves.

I see what the governments doing right now as very much opposite that. Frankly, when I look at the deficits of Congress, I see why. When I look at who is in the administration, the types of individuals that we have in Congress, I see very hard-working people doing what they feel is a terrific job. But there is just not the broad and deep field experience in the medical and health-care sectors.

TWP: Was it this perceived deficit that motivated you to run for Congress?

Keirstead:First and foremost, I see it as a continuation of my lifelong pursuits of trying to help people.

I see Congress as a larger stage to effect positive change. If I could have some positive influence in Congress, I could aid [those] that are trying to do good in the world but are having difficulty.

Let me give you an example: Im now expanding into brain cancer. Im running a Phase 2clinical trial with my team.I will not be able to do that if these policy changes of Trumps are instituted and a small company like mine is faced with double user fees. Its not in the budget. I cant ask an investor for another half of a million dollars for an administrative fee.

I see the administration putting insurmountable challenges in front of small businesses. Im about generating treatments to help people, putting medicines in peoples homes. And Im looking to the future and seeing that tap shut off.

Read more:

As scientists erupt in protest, a volcanologist runs for Congress

This group wants to fight anti-science rhetoric by getting scientists to run for office

Tens of thousands marched for science. Now what?

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Guide to Determining Viability and Concentration of Stem Cells Grown on Microcarriers – AZoM

Posted: at 9:47 am

Table of Content

Introduction Precise Counting of Adipose-Derived Mesenchymal Stem Cells Counting and Viability of Hematopoietic Stem Cells Counting Cells Growing on Microcarriers Cell Count Determination in Spheroids

Stem cell research and the significant potentials in stem cell therapy show a great deal of promise in 21st century medical treatments. Since stem cells typically need specialized conditions in culturing, knowing the concentration and capability of stem cells can be challenging.

Precise techniques for the determination of cell concentration and viability are needed to confirm consistency and reproducibility in stem cell culture. A wide range of specialized assays satisfying the needs of dedicated stem cell laboratories are offered by NucleoCounter instruments.

For reproducibility in stem cell research and production, detailed determination of cell viability and concentration is very crucial. Enhanced protocols are included in the NucleoCounter instruments to establish the count and viability of adipose-derived mesenchymal stem cells (MSC), that develop on microcarriers, and hematopoietic stem cells (HSC) found in the peripheral blood mononuclear cell (PBMC) fraction directly from whole blood and cell count determinations in spheroids.

Figure 1. Counting mononuclear cells including adipose-derived MSC in the stromal vascular fraction. (A) The stromal vascular fraction contains beside MSC, preadipocytes, endothelial cells and leukocytes also micelles, liposomes and microvesicles. By the use of Solution 10 the cells and the artifacts will be dissolved and the membranes permeabilized allowing for staining of nuclei with DAPI. (B) Image cytometry of cells stained with DAPI shows only the nucleated cells. (C) The accompanying NucleoView software allows the user to verify that all cells have been counted correctly.

A great deal of interest is produced by MSC from the stromal vascular fraction since these multipotent stem cells can be easily accessed and can be refined in large numbers directly from adipose tissue. Apart from MSC, leukocytes, preadipocytes, and endothelial cells are found in the stromal vascular fraction, as well as micelles, liposomes, and microvesicles.

It is a challenge to establish the cell count and viability of these newly isolated mononuclear cells, since liposomes, microvesicles, and micelles can be easily mistaken for cells while manually counting or when using automated cell counters.

To solve this issue, the NucleoCounter series instruments, NC-250, NC-200, and NC-3000, count only nucleated cells, as illustrated in Figure 1. After a lysis buffer is added, cells and other artifacts are lysed and thus, only the free nuclei in suspension are left out for staining with DAPI and for counting with the NucleoCounter systems.

Figure 2. Cell count and viability determination of PBMC from whole blood using the Viability and Cell Count Blood Assay. (A) Blood samples contain MSC, red blood cells, platelets and leukocytes, including HSC. Solution 17 will lyse red blood cells to minimize the quenching effect of the hemoglobin and to ensure robust staining of PBMC with Acridine Orange and DAPI to detect the total and dead cells respectively. Platelets are not stained due to the lack of nuclei and the weak staining. (B) Image cytometry of a stained whole blood sample shows the total count (green) and the dead count (blue). (C) The accompanying NucleoView software allows the user to verify that all cells have been counted correctly.

Until now, allogenic or autologous stem cell transplantations for the treatment of blood or bone cancer such as leukemia or myeloma, HSCs have been often used. All blood cells are produced by these stem cells and their purification can be easily performed from different sources such as peripheral blood and umbilical cord blood from the PBMC fraction.

Automated cell counters operating according to bright field cannot adequately distinguish between red blood cells and PBMC, and since the patient material still comprises of red blood cells, it becomes hard to determine the cell count and viability of newly isolated PBMC.

The NucleoCounter instruments NC-250, NC-200, and NC-3000 will count only PBMC, and will not count red blood cells and platelets, as they are faintly stained. To manage a high concentration of red blood cells, the NucleoCounter instrument offers Viability and Cell Count Blood Assay for whole blood, as illustrated in Figure 2.

In this blood assay, samples are incubated in Solution 17 to lyse the red blood cells and to confirm intense staining of the PBMC. The basic Viability and Cell Count Assay can be used to process the purified HSC.

Figure 3. Cell count and viability determination of cells growing on microcarriers. (A) The addition of reagent A100 and B lyses the cells bringing the nuclei into suspension. The total number of cells will be stained with DAPI and can be detected by the NucleoCounter family instruments NC-200, NC-250 and NC-3000. Afterwards, the dead count will be determined. (B) Image cytometry of cells stained with DAPI shows only the nucleated cells. (C) The accompanying NucleoView software allows the user to verify that all cells have been counted correctly.

The increasing demand in stem cell therapy and stem cell research is further compelled by the growing need for mass productions of human cells. To overcome these issues, mass productions leverage microcarriers, which are support matrix used for growing adherent cells such as mesenchymal stem cells (MSC).

Establishing the viability and concentration of cells, which are grown on microcarriers, is a highly complicated process, where cells have to be detached with trypsin that generally takes a lot of time. NC-250, NC-3000, and NC-200 offer a special protocol to count and determine the viability of cells, which are grown on microcarriers and that too without the need for earlier detachment, as shown in Figure 3.

Cells are lysed using the Viability and Cell Count A100 and B Assay that brings the nuclei into suspension. DAPI is used to stain all the cells and these are detected using the NucleoCounter instruments.

Later, DAPI is used again to stain the non-viable cells without any need for pretreatment, supposing that the dead cells without cell adhesions are not linked to the microcarriers and are freely suspended.

Figure 4. Cell count determination in spheroids. (A) Cells growing in spheroids will be heavily aggregated. By the use of Solution A100 and B, spheroids will be disaggregated and the membranes permeabilized allowing for staining of nuclei with DAPI. (B) Image cytometry of cells stained with DAPI shows the total cell count. C) The accompanying NucleoView software allows the user to verify that all cells have been counted correctly.

The physiological environment in organisms is usually replicated using the 3D culture of multicellular spheroids. Embryonic stem cells (ES) are actually forming embryoid bodies, and spheroids are formed during chondrogenic differentiation of mesenchymal stem cells (MSC) in vitro.

The manual counting process or automated cell counter cannot be used to establish the total cell count of spheroids, because separate cells cannot be distingushed. The NucleoCounter instruments such as NC-250, NC-200, and NC-3000 are offered with an assay that is primarily made for spheroids (refer Figure 4).

The application of the Count of Aggregated Cells A100 and B Assay makes it easy to break-up the spheroids and so guarantees an even sample of single nuclei. DAPI can be used to stain these nuclei, and the NucleoCounter system can be employed to detect them.

Source

Stem Cells Counting

This information has been sourced, reviewed and adapted from materials provided by ChemoMetec A/S.

For more information on this source, please visit ChemoMetec A/S.

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