Category Archives: Stem Cells

16 hours ago by Denis Paiste MIT biological engineering graduate student Frances Liu works with a spiral-shaped inertial microfluidic separation device for separating stem cell populations in the Laboratory for Material Chemomechanics at MIT. This device was adapted from previous designs to separate cells as a function of diameter. Liu also grows bone marrow-derived stem cells and studies how those stem cells release certain chemicals in response to mechanical interactions with materials in the surrounding environment. Credit: Denis Paiste/Materials Processing Center

Researchers in MIT Associate Professor Krystyn J. Van Vliet's group last year showed that three biomechanical and biophysical markers could accurately identify the most desirable stem cells from a mixed group of bone marrow-derived cells. Now, MIT biological engineering graduate student Frances Liu is trying to advance that work by understanding how to alter the stem cells' physical environment to get them to produce the most desirable chemical output.

The bone marrow cells secrete special chemicals called cytokines that are needed in the body to repair bone tissue, fat tissue, and connective tissue like cartilage. "These so-called factors that the cells produce are associated with those tissue growth functions and tissue repair functions," Van Vliet says.

Liu grows bone marrow-derived stem cells and studies how those stem cells release certain chemicals in response to mechanical interactions with materials in their surrounding environment. "I would like to manipulate the cells, using cell-material interactions, or synthetic materials, to produce certain chemicals beneficial to tissue repair," Liu explains in the Laboratory for Material Chemomechanics at MIT. "Right now we are in the characterization phase, quantifying which and how much of different cytokines the cells secrete in response to different chemical and mechanical cues that we provide. Down the line, we aim to engineer those cytokine profiles using cell-material interactions." Liu, 24, is a third-year PhD student and expects to complete her doctorate in 2017. She received her bachelor of science degree in biomedical engineering from Brown University.

Liu is examining how various groups of stem cells differ in response to lab-controlled changes in their environment in ways that might be important for tissue repair in the body. "Frances is determining the correlations between the mechanical properties of the materials the cells interact with and the chemical factors that they produce in response to that chemomechanical coupling," Van Vliet says.

Heterogeneous cellular factories

"You can think of the cells as factories; they're factories of chemicals," Van Vliet explains. "One of the main ways you change the way that factory operates is you change the material properties of its environment. How stiff that environment is, how acidic that environment is, how rough that environment is, all of those characteristics of the cell's outside world can directly correlate with the chemicals that that cell produces. We don't really understand all of why that happens yet, but part of Frances' thesis is to understand these particular stem cells and the subpopulations within them."

While other researchers previously studied mechanical factors such as stiffness on the function of these mesenchymal (bone marrow-derived) stem cells, it wasn't widely recognized that they were examining a mixed population of cells, not a single well-defined cell population. "Some of them were stem cells, but some were not," Van Vliet says.

One way that Liu sorts her stem cells into groups is using an inertial microfluidic separation device that separates cells of large diameter cells from those of small diameter. This device was adapted from previous designs of their collaborator, MIT Professor Jongyoon Han, as part of the interdisciplinary team that Van Vliet leads within the Singapore-MIT Alliance for Research and Technology (SMART). The group showed in a 2014 paper that three markerssize, mechanical stiffness, and how much the nucleus inside the cell moves aroundare sufficient to identify stem cells in a heterogeneous population of chemically similar but non-stem cells. "We measured those three properties as well as several other properties, but only those three properties together, that triplet of properties, distinguished a stem cell from a non-stem cell," Van Vliet says.

By using the microfluidic device, we can better understand the differences between the subpopulations of these heterogeneous bone marrow cells and which cytokines each subpopulation may be secreting, both in the body and in the lab.

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Altering mechanical properties of cell environments to produce desired chemical outputs

FREDERICK, Md., March 23, 2015 /PRNewswire-USNewswire/ --Recent studies employing adult stem cells obtained from bone marrow and fat have been used in patients suffering from osteoarthritis of the knee. Results have indicated not only symptomatic improvement but also suggest that cartilage healing and regeneration may be taking place.

According to Director, Dr. Nathan Wei of the Arthritis Treatment Center, "Osteoarthritis options in the past have been limited to symptom relief. We are now entering an era where we have therapies that may also rebuild lost cartilage."

Osteoarthritis (OA) of the knee affects more than 20 million Americans. It is a disease due to loss of cartilage, the gristle that caps the ends of long bones and provides cushioning and shock absorption.

He goes on to say, "by administering adult stem cells, in a certain fashion, we may be able to restore lost cartilage. While this action has been demonstrated in multiple animal models, it has only been described in anecdotal reports in humans. Fortunately, we are now conducting clinical studies that are much better controlled and more scientifically valid."

Dr. Wei adds, "The positive effect on arthritis is not only due to multiplication, division, and transformation of the stem cell into cartilage, but it is also due to the fact the stem cell releases proteins that attract other reparative cells to the area. This is called the 'paracrine' effect."

"We are excited about the early results of our investigation and hope the results will continue to be positive. If so, I hope that knee replacement surgery might become a thing of the past," he concludes.

Dr. Wei is a board-certified rheumatologist and regenerative medicine expert. He is director of the Arthritis Treatment Center located in Frederick, Maryland.

SOURCE Arthritis Treatment Center

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Stem cell treatment for knee arthritis shows promising results

The pioneering treatment involves cells taken from a patients own body Theseare then reinjected into their heart to repair damaged muscle Could improve quality of life for patients suffering from heart failure This is caused by heart failing to pump enough blood around the body at the right pressure

By Roger Dobson and Katherine Keogh For The Mail On Sunday

Published: 17:16 EST, 21 March 2015 | Updated: 18:15 EST, 21 March 2015

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A pioneering treatment that uses stem cells to repair a broken heart could transform the lives of people with a potentially fatal cardiac condition.

The 15-minute procedure involves cells taken from a patients own body, which are then reinjected into their heart to repair damaged muscle.

It is hoped that the procedure could improve the quality of life for patients suffering from heart failure, which affects 900,000 people in the UK.

The condition is caused by the heart failing to pump enough blood around the body at the right pressure, because the muscle has become too weak or stiff to work properly. It causes breathlessness and extreme tiredness, and can even lead to sudden death.

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How stem cells can fix a broken heart with just one jab

Scientists at the University of California, Berkeley, have identified a new molecular pathway critical to aging, and confirmed that the process can be manipulated to help make old blood like new again.

The researchers found that blood stem cells' ability to repair damage caused by inappropriate protein folding in the mitochondria, a cell's energy station, is critical to their survival and regenerative capacity.

The discovery, to be published in the March 20 issue of the journal Science, has implications for research on reversing the signs of aging, a process thought to be caused by increased cellular stress and damage.

"Ultimately, a cell dies when it can't deal well with stress," said study senior author Danica Chen, an assistant professor in the Department of Nutritional Sciences and Toxicology. "We found that by slowing down the activity of mitochondria in the blood stem cells of mice, we were able to enhance their capacity to handle stress and rejuvenate old blood. This confirms the significance of this pathway in the aging process."

Mitochondria host a multitude of proteins that need to be folded properly to function correctly. When the folding goes awry, the mitochondrial unfolded-protein response, or UPRmt, kicks in to boost the production of specific proteins to fix or remove the misfolded protein.

Chen's lab stumbled upon the importance of UPRmt in blood stem cell aging while studying a class of proteins known as sirtuins, which are increasingly recognized as stress-resistance regulators.

The researchers noticed that levels of one particular sirtuin, SIRT7, increase as a way to help cells cope with stress from misfolded proteins in the mitochondria. Notably, SIRT7 levels decline with age.

There has been little research on the UPRmt pathway, but studies in roundworms suggest that its activity increases when there is a burst of mitochondrial growth.

Chen noted that adult stem cells are normally in a quiescent, standby mode with little mitochondrial activity. They are activated only when needed to replenish tissue, at which time mitochondrial activity increases and stem cells proliferate and differentiate. When protein-folding problems occur, however, this fast growth could lead to more harm.

"We isolated blood stem cells from aged mice and found that when we increased the levels of SIRT7, we were able to reduce mitochondrial protein-folding stress," said Chen. "We then transplanted the blood stem cells back into mice, and SIRT7 improved the blood stem cells' regenerative capacity."

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Even at a molecular level, taking it slow helps us cope with stress

(Source: Thinkstock; art by Tanya Leigh Washington)

We're no strangerswhen it comes to wild beauty products. Snail venom, check. Probiotic bacteria, of course. Charcoal, yes, please. But when we started noticing stem cells popping up as ingredients in beauty products, we raised an eye brow.

First off, these aren't the stem cells that have caused a lot of controversy in recent years. These are (typically) stem cells extracts from plants andfruits and are believed by some to encourage cell regeneration, restoration and repair. However, some products are using human stem cell derived proteins as active ingredients. The basic idea is this:stem cell extracts uppotential growth for collagen and elastinyou know, those tissues that keep us looking youthful.

Althoughthe jury is still out on the effectiveness of stem cell-based products, one thing's for surethispossible fountain of youth comes at a steep price tag. Due to the extraction and cultivation process of stem cell extracts, products tend to be on the higher end side.

If stem cell technology sounds like something you're ready to invest in, take a peek at a view of the products on the market that caught our eyes.

Rodial Stemcell Super-Food Cleanser, $40, atus.spacenk.com

Stem cell technology from thePhytoCellTec Alp Rose mixed with Coconut Oil, Rose Hip Oil, Rose Wax and Cocoa Butter hydrate and cleanses.

Juice Beauty Stem Cellular Lifting Neck Cream, $55, atjuicebeauty.com

This blend of fruit stem cells are infused into a Vitamin C, resveratrol rich grapeseed formula to provide antioxidant protection and firm up skin.

StemologyCell Revive Smoothing Serum, $99, at stemologyskincare.com

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Why Stem Cell Beauty Products are Causing a Buzz in Anti-Aging

New York, March 20 (IANS): High stress levels can have a critical impact not only on the surface, making our skin age, but also on a molecular level, when stressed cells cannot cope with the pressure and perish much faster than the ones which can.

In a new research report released on Thursday, scientists at the University of California, Berkeley, analysed blood stem cells and found that the cell's ability to repair damage in the mitochondria, their power source, was critical to their survival.

Researchers tried to "relax" these stressed-out cells by slowing down the activity of their mitochondria.

"We found that by slowing down the activity of mitochondria in the blood stem cells of mice, we were able to enhance their capacity to handle stress and rejuvenate old blood. This confirms the significance of this pathway in the aging process," Xinhua news agency quoted Danica Chen, an assistant professor with the Department of Nutritional Sciences and Toxicology.

This pathway lies mainly in the multitude of proteins that need to be folded properly for the mitochondria to function correctly. When the folding goes awry, the mitochondrial unfolded-protein response, or UPRmt, kicks in to boost the production of specific proteins to fix or remove the misfolded protein.

Researchers found that certain proteins known as SIRT7 help cells cope with the stress of unfolding the proteins in the mitochondria, helping those with higher levels of SIRT7 survive longer by making them "unwind". But the levels of SIRT7 decrease as people age.

"The protein level decreases as years go by," Chen said. "But if we increase this protein in blood stem cells, we can make them live longer. Cells in general don't just die suddenly; they are submitted to high stress levels and lose their functions with age."

Chen does not want to encourage the thought that she and other researchers have found the "fountain of youth", but more of a new path for study.

"We still don't know if this would work on other kinds of stem cells, such as pancreatic stem cells or heart cells, and we don't have any expertise with those tissues, so we would be very happy to collaborate with other laboratories to tackle the matter," she said.

The study, published on Thursday in the Science journal, is expected to help researchers gain more insight into the aging process, and even slow it down.

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Fountain of youth might hide in 'relaxed' stem cells: Study

Targeting Cancer Cells and Stem Cells with Dietary Lupeol
Jordan Davis and Gygeria Manuel. Targeting Cancer Cells and Stem Cells with Dietary Lupeol.

By: Jordan Davis

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Targeting Cancer Cells and Stem Cells with Dietary Lupeol - Video

Scientists at the University of Cambridge have successfully created 'mini-lungs' using stem cells derived from skin cells of patients with cystic fibrosis, and have shown that these can be used to test potential new drugs for this debilitating lung disease.

The research is one of a number of studies that have used stem cells - the body's master cells - to grow 'organoids', 3D clusters of cells that mimic the behaviour and function of specific organs within the body. Other recent examples have been 'mini-brains' to study Alzheimer's disease and 'mini-livers' to model liver disease. Scientists use the technique to model how diseases occur and to screen for potential drugs; they are an alternative to the use of animals in research.

Cystic fibrosis is a monogenic condition - in other words, it is caused by a single genetic mutation in patients, though in some cases the mutation responsible may differ between patients. One of the main features of cystic fibrosis is the lungs become overwhelmed with thickened mucus causing difficulty breathing and increasing the incidence of respiratory infection. Although patients have a shorter than average lifespan, advances in treatment mean the outlook has improved significantly in recent years.

Researchers at the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute used skin cells from patients with the most common form of cystic fibrosis caused by a mutation in the CFTR gene referred to as the delta-F508 mutation. Approximately three in four cystic fibrosis patients in the UK have this particular mutation. They then reprogrammed the skin cells to an induced pluripotent state, the state at which the cells can develop into any type of cell within the body.

Using these cells - known as induced pluripotent stem cells, or iPS cells - the researchers were able to recreate embryonic lung development in the lab by activating a process known as gastrulation, in which the cells form distinct layers including the endoderm and then the foregut, from which the lung 'grows', and then pushed these cells further to develop into distal airway tissue. The distal airway is the part of the lung responsible for gas exchange and is often implicated in disease, such as cystic fibrosis, some forms of lung cancer and emphysema.

The results of the study are published in the journal Stem Cells and Development.

"In a sense, what we've created are 'mini-lungs'," explains Dr Nick Hannan, who led the study. "While they only represent the distal part of lung tissue, they are grown from human cells and so can be more reliable than using traditional animal models, such as mice. We can use them to learn more about key aspects of serious diseases - in our case, cystic fibrosis."

The genetic mutation delta-F508 causes the CFTR protein found in distal airway tissue to misfold and malfunction, meaning it is not appropriately expressed on the surface of the cell, where its purpose is to facilitate the movement of chloride in and out of the cells. This in turn reduces the movement of water to the inside of the lung; as a consequence, the mucus becomes particular thick and prone to bacterial infection, which over time leads to scarring - the 'fibrosis' in the disease's name.

Using a fluorescent dye that is sensitive to the presence of chloride, the researchers were able to see whether the 'mini-lungs' were functioning correctly. If they were, they would allow passage of the chloride and hence changes in fluorescence; malfunctioning cells from cystic fibrosis patients would not allow such passage and the fluorescence would not change. This technique allowed the researchers to show that the 'mini-lungs' could be used in principle to test potential new drugs: when a small molecule currently the subject of clinical trials was added to the cystic fibrosis 'mini lungs', the fluorescence changed - a sign that the cells were now functioning when compared to the same cells not treated with the small molecule.

"We're confident this process could be scaled up to enable us to screen tens of thousands of compounds and develop mini-lungs with other diseases such as lung cancer and idiopathic pulmonary fibrosis," adds Dr Hannan. "This is far more practical, should provide more reliable data and is also more ethical than using large numbers of mice for such research."

Continued here:
Scientists grow 'mini-lungs' to aid the study of cystic fibrosis

Scientists at the University of Cambridge have successfully created 'mini-lungs' using stem cells derived from skin cells of patients with cystic fibrosis, and have shown that these can be used to test potential new drugs for this debilitating lung disease.

The research is one of a number of studies that have used stem cells -- the body's master cells -- to grow 'organoids', 3D clusters of cells that mimic the behaviour and function of specific organs within the body. Other recent examples have been 'mini-brains' to study Alzheimer's disease and 'mini-livers' to model liver disease. Scientists use the technique to model how diseases occur and to screen for potential drugs; they are an alternative to the use of animals in research.

Cystic fibrosis is a monogenic condition -- in other words, it is caused by a single genetic mutation in patients, though in some cases the mutation responsible may differ between patients. One of the main features of cystic fibrosis is the lungs become overwhelmed with thickened mucus causing difficulty breathing and increasing the incidence of respiratory infection. Although patients have a shorter than average lifespan, advances in treatment mean the outlook has improved significantly in recent years.

Researchers at the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute used skin cells from patients with the most common form of cystic fibrosis caused by a mutation in the CFTR gene referred to as the delta-F508 mutation. Approximately three in four cystic fibrosis patients in the UK have this particular mutation. They then reprogrammed the skin cells to an induced pluripotent state, the state at which the cells can develop into any type of cell within the body.

Using these cells -- known as induced pluripotent stem cells, or iPS cells -- the researchers were able to recreate embryonic lung development in the lab by activating a process known as gastrulation, in which the cells form distinct layers including the endoderm and then the foregut, from which the lung 'grows', and then pushed these cells further to develop into distal airway tissue. The distal airway is the part of the lung responsible for gas exchange and is often implicated in disease, such as cystic fibrosis, some forms of lung cancer and emphysema.

The results of the study are published in the journal Stem Cells and Development.

"In a sense, what we've created are 'mini-lungs'," explains Dr Nick Hannan, who led the study. "While they only represent the distal part of lung tissue, they are grown from human cells and so can be more reliable than using traditional animal models, such as mice. We can use them to learn more about key aspects of serious diseases -- in our case, cystic fibrosis."

The genetic mutation delta-F508 causes the CFTR protein found in distal airway tissue to misfold and malfunction, meaning it is not appropriately expressed on the surface of the cell, where its purpose is to facilitate the movement of chloride in and out of the cells. This in turn reduces the movement of water to the inside of the lung; as a consequence, the mucus becomes particular thick and prone to bacterial infection, which over time leads to scarring -- the 'fibrosis' in the disease's name.

Using a fluorescent dye that is sensitive to the presence of chloride, the researchers were able to see whether the 'mini-lungs' were functioning correctly. If they were, they would allow passage of the chloride and hence changes in fluorescence; malfunctioning cells from cystic fibrosis patients would not allow such passage and the fluorescence would not change. This technique allowed the researchers to show that the 'mini-lungs' could be used in principle to test potential new drugs: when a small molecule currently the subject of clinical trials was added to the cystic fibrosis 'mini lungs', the fluorescence changed -- a sign that the cells were now functioning when compared to the same cells not treated with the small molecule.

"We're confident this process could be scaled up to enable us to screen tens of thousands of compounds and develop mini-lungs with other diseases such as lung cancer and idiopathic pulmonary fibrosis," adds Dr Hannan. "This is far more practical, should provide more reliable data and is also more ethical than using large numbers of mice for such research."

Originally posted here:
Scientists grow 'mini-lungs' to aid study of cystic fibrosis

4 hours ago By labeling a piece of a stem cell superenhancer, which is a gene amplifying region, researchers made stem cells fluoresce in green in living mice. The cells are visible above lining the base of the two hair follicles. Although they do not contain stem cells, the hair shafts also fluoresce green.

Stem cells can have a strong sense of identity. Taken out of their home in the hair follicle, for example, and grown in culture, these cells remain true to themselves. After waiting in limbo, these cultured cells become capable of regenerating follicles and other skin structures once transplanted back into skin. It's not clear just how these stem cells and others elsewhere in the body retain their ability to produce new tissue and heal wounds, even under extraordinary conditions.

New research at Rockefeller University has identified a protein, Sox9, that takes the lead in controlling stem cell plasticity. In a paper published today (March 18) in Nature, the team describes Sox9 as a "pioneer factor" that breaks ground for the activation of genes associated with stem cell identity in the hair follicle.

"We found that in the hair follicle, Sox9 lays the foundation for stem cell plasticity. First, Sox9 makes the genes needed by stem cells accessible, so they can become active. Then, Sox9 recruits other proteins that work together to give these "stemness" genes a boost, amplifying their expression," says study author Elaine Fuchs, Rebecca C. Lancefield Professor, Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development. "Without Sox9, this process never happens, and hair follicle stem cells cannot survive."

Sox9 is a type of protein called a transcription factor, which can act like a volume dial for genes. When a transcription factor binds to a segment of DNA known as an enhancer, it cranks up the activity of the associated gene. Recently, scientists identified a less common, but more powerful version: the super-enhancer. Super-enhancers are much longer pieces of DNA, and host large numbers of cell type-specific transcription factors that bind cooperatively. Super-enhancers also containhistones, DNA-packagingproteins, that harbor specific chemical groups epigenetic marks that make genes they are associated with accessible so they can be expressed.

Using an epigenetic mark associated specifically with the histones of enhancers, first author Rene Adam, a graduate student in the lab, and colleagues, identified 377 of these high-powered gene-amplifying regions in hair follicle stem cells. The majority of these super-enhancers were bound by at least five transcription factors, often including Sox9. Then, they compared the stem cell super-enhancers to those of short-lived stem cell progeny, which have begun to choose a fate, and so lost the plasticity of stem cells. These two types of cells shared only 32 percent of their superenhancers, suggesting these regions played an important role in skin cell identity. By switching off super-enhancers associated with stem cell genes, these genes were silenced while new super-enhancers were being activated to turn on hair genes.

To better understand these dynamics, the researchers took a piece of a super-enhancer, which they called an "epicenter," where all the stem cell transcription factors bind, and they linked it to a gene thatglowed green whenever the transcription factors were present. In living mice, all the hair follicle stem cells glowed green, but surprisingly, the green gene turned off when the stem cells were taken from the follicle and placed in culture. When they put the cells back into living skin, the green glow returned.

Another clue came from experiments performed by Hanseul Yang, another student in the lab. By examining the new super-enhancers that were gained when the stem cells were cultured, they learned that these new super-enhancers bound transcription factors that were known to be activated during wound-repair. When they used one of these epicenters to drive the green gene, the green glow was seen in culture, but not in skin. When they wounded the skin, then the green glow switched on.

"We were learning that some super-enhancers are specifically activated in the stem cells within their native niche, while other super-enhancers specifically switch on during injury," explained Adam. "By shifting epicenters, you can shift from one cohort of transcription factors to another to adapt to different environments. But we still needed to determine what was controlling these shifts."

The culprit turned out to be Sox9, the only transcription factor expressed in both living tissue and culture. Further experiments confirmed Sox9's importance by showing, for example, that removing it spelled death for stem cells, while expressing it in the epidermis gave the skin cells features of hair follicle stem cells. These powers seemed to be special to Sox9, placing it atop the hierarchy of transcription factors in the stem cells. Sox9 is one of only a few pioneer factors known in biology which can initiate such dramatic changes in gene expression.

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Scientists pinpoint molecule that controls stem cell plasticity by boosting gene expression