(Boston)--Using patient-derived stem cells known as induced pluripotent stem cells (iPSC) to study the genetic lung/liver disease called alpha-1 antitrypsin (AAT) deficiency, researchers have for the first time created a disease signature that may help explain how abnormal protein leads to liver disease.

The study, which appears in Stem Cell Reports, also found that liver cells derived from AAT deficient iPSCs are more sensitive to drugs that cause liver toxicity than liver cells derived from normal iPSCs. This finding may ultimately lead to new treatments for the condition.

IPSC's are derived from the donated skin or blood cells of adults and, with the reactivation of four genes, are reprogrammed back to an embryonic stem cell-like state. Like embryonic stem cells, iPSC can be differentiated toward any cell type in the body, but they do not require the use of embryos. Alpha-1 antitrypsin deficiency is a common genetic cause of both liver and lung disease affecting an estimated 3.4 million people worldwide.

Researchers from the Center for Regenerative Medicine (CReM) at Boston University and Boston Medical Center (BMC) worked for several years in collaboration with Dr. Paul Gadue and his group from Children's Hospital of Philadelphia to create iPSC from patients with and without AAT deficiency. They then exposed these cells to certain growth factors in-vitro to cause them to turn into liver-like cells, in a process that mimics embryonic development. Then the researchers studied these "iPSC-hepatic cells" and found the diseased cells secrete AAT protein more slowly than normal cells. This finding demonstrated that the iPSC model recapitulates a critical aspect of the disease as it occurs in patients. AAT deficiency is caused by a mutation of a single DNA base. Correcting this single base back to the normal sequence fixed the abnormal secretion.

"We found that these corrected cells had a normal secretion kinetic when compared with their diseased, parental cells that are otherwise genetically identical except for this single DNA base," explained lead author Andrew A. Wilson, MD, assistant professor of medicine at Boston University School of Medicine and Director of the Alpha-1 Center at Bu and BMC.

They also found the diseased (AAT deficient) iPSC-liver cells were more sensitive to certain drugs (experience increased toxicity) than those from normal individuals. "This is important because it suggests that the livers of actual patients with this disease might be more sensitive in the same way," said Wilson, who is also a physician in pulmonary, critical care and allergy medicine at BMC.

According to Wilson, while some patients are often advised by their physicians to avoid these types of drugs, these recommendations are not based on solid scientific evidence. "This approach might now be used to generate that sort of evidence to guide clinical decisions," he added.

The researchers believe that studies using patient-derived stem cells will allow them to better understand how patients with AAT deficiency develop liver disease. "We hope that the insights we gain from these studies will result in the discovery of new potential treatments for affected patients in the near future," said Wilson.

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Funding was provided by an ARRA stimulus grant (1RC2HL101535-01) awarded by the National Institutes of Health (NIH) to Boston University School of Medicine, Boston Medical Center and the Children's Hospital of Philadelphia. Additional funding was provided by K08 HL103771, FAMRI 062572_YCSA, an Alpha-1 Foundation Research Grant and a Boston University Department of Medicine Career Investment Award. Additional grants from NIH 1R01HL095993 and 1R01HL108678 and an ARC award from the Evans Center for Interdisciplinary Research at Boston University supported this work.

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Researchers produce iPSC model to better understand genetic lung/liver disease

Using patient-derived stem cells known as induced pluripotent stem cells (iPSC) to study the genetic lung/liver disease called alpha-1 antitrypsin (AAT) deficiency, researchers have for the first time created a disease signature that may help explain how abnormal protein leads to liver disease.

The study, which appears in Stem Cell Reports, also found that liver cells derived from AAT deficient iPSCs are more sensitive to drugs that cause liver toxicity than liver cells derived from normal iPSCs. This finding may ultimately lead to new treatments for the condition.

IPSC's are derived from the donated skin or blood cells of adults and, with the reactivation of four genes, are reprogrammed back to an embryonic stem cell-like state. Like embryonic stem cells, iPSC can be differentiated toward any cell type in the body, but they do not require the use of embryos. Alpha-1 antitrypsin deficiency is a common genetic cause of both liver and lung disease affecting an estimated 3.4 million people worldwide.

Researchers from the Center for Regenerative Medicine (CReM) at Boston University and Boston Medical Center (BMC) worked for several years in collaboration with Dr. Paul Gadue and his group from Children's Hospital of Philadelphia to create iPSC from patients with and without AAT deficiency. They then exposed these cells to certain growth factors in-vitro to cause them to turn into liver-like cells, in a process that mimics embryonic development. Then the researchers studied these "iPSC-hepatic cells" and found the diseased cells secrete AAT protein more slowly than normal cells. This finding demonstrated that the iPSC model recapitulates a critical aspect of the disease as it occurs in patients. AAT deficiency is caused by a mutation of a single DNA base. Correcting this single base back to the normal sequence fixed the abnormal secretion.

"We found that these corrected cells had a normal secretion kinetic when compared with their diseased, parental cells that are otherwise genetically identical except for this single DNA base," explained lead author Andrew A. Wilson, MD, assistant professor of medicine at Boston University School of Medicine and Director of the Alpha-1 Center at Bu and BMC.

They also found the diseased (AAT deficient) iPSC-liver cells were more sensitive to certain drugs (experience increased toxicity) than those from normal individuals. "This is important because it suggests that the livers of actual patients with this disease might be more sensitive in the same way," said Wilson, who is also a physician in pulmonary, critical care and allergy medicine at BMC.

According to Wilson, while some patients are often advised by their physicians to avoid these types of drugs, these recommendations are not based on solid scientific evidence. "This approach might now be used to generate that sort of evidence to guide clinical decisions," he added.

The researchers believe that studies using patient-derived stem cells will allow them to better understand how patients with AAT deficiency develop liver disease. "We hope that the insights we gain from these studies will result in the discovery of new potential treatments for affected patients in the near future," said Wilson.

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The above story is based on materials provided by Boston University Medical Center. Note: Materials may be edited for content and length.

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iPSC model helps to better understand genetic lung/liver disease

That's the promise of a high-end new facial treatment.

In a tiny room inside an Upper East Side dermatologist's office, I'm attempting to regain my youth. Or, at the very least, look better. I've come to try the HydraFacial, a multistep treatment that promises to erase wrinkles, reverse sun damage, lighten dark spots, and prevent acne. All of these transformations come from one key innovation using stem cells from an infant's foreskin to trick skin into behaving young again.

Why foreskin? Dr. Gail Naughton, a leader in regenerative science she developed technology to growhuman tissues and organs outside the body explains it this way: When we're born, our skin is in its best shape. Our cells naturally secrete proteins known as growth factors "that keep the cells healthy and stimulate them to divide," Naughton says. As we age, our cells divide at a slower rate, which contribute to the telltale signs of aging, like wrinkles and loss of firmness and luminosity. Growth factors captured from the donated foreskin of a baby (just one can generate over a million treatments) are at their peak ability in promoting rapid cell turnover. Applied topically, they spur adult skin cells to regenerate. This is said to have a smoothing effect on the skin.

I'm here to see if the process actually works specifically, on my nasolabial folds, the hereditary creases that stretch from my nose to my mouth. I'm told that three HydraFacial treatments will smooth the creases into near invisibility.

There are five parts to the HydraFacial. My skin is first wiped clean with a cleanser and then treated with a salicylic-and-glycolic-acid peel using a giant machine that looks like a cousin of R2D2. This is the HydraFacial machine, a fully equipped device with tiny suction tubes as arms and bottles of facial-treatment mixtures attached at the belly.

The salicylicand glycolic acids, like micro sandblasters, sweep away dead cells lingering on the surface of skin. The chemicals are a lightweight goop that feels cool on my face. Zahra, my esthetician, keeps asking me if I feel any tingling on my skin. I don't but she tells me that most people feel a slight burning sensation at this point. Must be my thick skin.

Next up is the extraction step. The tube that deposited the peel now works in reverse and becomes a micro vacuum cleaner. Blackheads and flaky skin are swept up in what feel (and looks) like the suction tube from a dentist's chair. It's an odd but not unpleasant feeling. I can actually see tiny deposits of my skin now swirling around in the extraction cup. Gross, but also kind of cool.

After my pores are cleared, a blend of skin-nourishing antioxidants and hydrating hyaluronic acid is smeared over my face. Here's where the foreskin extracts come in they're smeared on, too. The growth factors from the foreskin stem cells don't feel different than any other serum as the esthetician applies them to my face.

The final step of the facial is a quick, light therapy session, where a blue and red LED light targets oily skin, fine lines, and hyperpigmentation. In all, the entire facial lasts 30 minutes and induces not the faintest trace of redness or irritation.

Of course when it comes to facials, the proof is in the mirror. My skin glows in a way that I thought only Jennifer Lopez could glow. Fresh from the facial, I saunter into a photo shoot wearing no makeup because my confidence is at Beyonc levels. My nasolabial folds are still visible, although a bit less pronounced now. (Presumably, two more treatments would help even more.) And a part of me feels like a Disney evil queen, draining youth from a newborn for a few weeks of a restored complexion. Is this the future of facials? And if so, is it wrong that I want more?

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Can Cells From a Babys Foreskin Give You Youthful Skin?

$1 M gift from Mr. J. Sebastian van Berkom launches translational research into neurological disease

This news release is available in French.

A patient's very own skin cells may hold the key to new treatments and even cures for devastating neurological diseases. A generous $1 million donation from Mr. J. Sebastian van Berkom, and critical partnerships with Brain Canada, Laval University, Marigold Foundation and the FRQS-Rseau Parkinson Quebec are driving an innovative, iPSC (induced pluripotent stem cell) research platform that will transform research into Parkinson's and other neurological diseases.

Millions of Canadians are affected by diseases of the brain such as ALS, Parkinson's and brain tumours, for which there are limited treatments and no cures. By 2020, neurological conditions will become the leading cause of death and disability. "Everyone's lives are touched in some way by neurological disease, says Mr. van Berkom, President of Van Berkom and Associates Inc." In creating The van Berkom Parkinson's Disease Open-Access Fund, I hope to change lives and support new research that will lead to new treatments and one day cures. The iPSC platform is a new paradigm for neuroscience research and as one of the world's great neuroscience centres, The Neuro is the place to drive it forward."

"This is the ultimate bench to bedside paradigm, from patient to the bench, back to the patient," says Dr. Guy Rouleau, Director of The Neuro. "With a unique interface between fundamental and clinical research, The Neuro is uniquely positioned to be a central hub in the iPSC platform. Partnering with Mr. Van Berkom, a generous and visionary philanthropist, propels The Neuro toward the goal of significantly deepening insight into disease mechanisms with unprecedented efficiency."

Patients' skin cells will be reprogrammed into induced pluripotent stem cells (iPSCs) at Laval University, under the leadership of Dr Jack Puymirat, and then differentiated at The Neuro into disease relevant cells for research. For example, in the case of Parkinson's this could be dopamine neurons. The cells can also be genome-edited, a state-of-the-art technique that can introduce or correct disease associated mutations - creating the most accurate disease models. These iPSCs will be made widely and openly available to researchers across Quebec for neuroscience research. This open-access approach exponentially increases the likelihood of breakthroughs in neurological disease.

"The unique and exciting aspect of this platform is that we are creating the most specific cells for studying disease using the patient's own tissue, which has distinct advantages over using generic cells or animal models," says Dr. Edward Fon, neurologist and co-Director of the Quebec iPSC platform. "Disease models using human samples are increasingly shown to be far more efficacious in trials, as they much more accurately mimic the disease condition. In the iPSC platform, not only can specific mutations be introduced but, cells are from patients' whose specific clinical history and genetic profile are known, a first step on the road toward neurological personalized medicine. The Neuro has access to a large and well-characterized patient population, who can help create a rich clinically-and genetically-derived registry and biobank. The initial targets in the platform will be ALS and Parkinson's disease (PD), using dopamine neurons for PD and both motor neurons and astrocytes for ALS."

The Quebec iPSC core facility is a provincial core headed by Drs. Fon and Puymirat. Reprogrammed cells at Laval University will be created from different sources such as skin biopsies, blood or urine. The Neuro's component of the platform will consist of two core facilities. The iPSC neuronal differentiation core - which differentiate iPSCs into functional neurons, headed by Dr. Eric Shoubridge, and the iPSC genome-editing core providing unprecedented ability to study the influence of disease mutations, headed by Dr. Peter McPherson.

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The Montreal Neurological Institute and Hospital

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Using patients' own cells to accelerate research into neurological disease

Durham, NC (PRWEB) March 31, 2015

Stem cells may provide Crohns disease sufferers relief from a common, potentially dangerous side effect fistulas according to the results of a phase 2 clinical trial published in the latest issue of STEM CELLS Translational Medicine (SCTM). After receiving an injection of their own adipose-derived stem cells (ASC), which are collected from fat tissue, the fistulas in 75 percent of the trial participants were completely healed within eight weeks of their last treatment and remained so two years later.

Crohn's disease is a painful, chronic autoimmune disorder in which the body's immune system attacks the gastrointestinal tract. Inflammation in Crohns patients can sometimes extend completely through the intestinal wall and create a fistula an abnormal connection between the intestine and another organ or skin. Left untreated, a fistula might become infected and form an abscess, which in some cases can be life threatening.

Chang Sik Yu, M.D., Ph.D., of Asan Medical Center in Seoul, Korea, a senior author of the SCTM paper, describes the results of a clinical trial conducted in collaboration with four other hospitals in South Korea, stated, Crohns fistula is one of the most distressing diseases as it decreases patients quality of life and frequently recurs. It has been reported to occur in up to 38 percent of Crohns patients and over the course of the disease, 10 to 18 percent of them must undergo a proctectomy, which is a surgical procedure to remove the rectum.

Overall, the treatments currently available for Crohns fistula remain unsatisfactory because they fail to achieve complete closure, lower recurrence and limit adverse effects, Dr. Yu said. Given the challenges and unmet medical needs in Crohns fistula, attention has turned to stem cell therapy as a possible treatment.

Several studies, including those undertaken by Dr. Yus team, suggest that mesenchymal stem cells (MSCs) do indeed improve Crohns disease and Crohns fistula. Their phase II trial involved 43 patients for a term of one year, over the period from January 2010 to August 2012. The results showed that 82 percent experienced complete closure of fistula eight weeks after the final ASC injection.

It strongly demonstrated MSCs derived from ASCs are a safe and useful therapeutic tool for the treatment of Crohns fistula, Dr. Yu said.

The latest study was intended to evaluate the long-term outcome by following 41 of the original 43 patients for yet another year. Dr. Yu reported, Our long-term follow-up found that one or two doses of autologous ASC therapy achieved complete closure of the fistulas in 75 percent of the patients at 24 months, and sustainable safety and efficacy of initial response in 83 percent. No adverse events related to ASC administration were observed. Furthermore, complete closure after initial treatment was well sustained.

These results strongly suggest that autologous ASCs may be a novel treatment option for Crohns fistulae, he said.

Stem cells derived from fat tissue are known to regulate the immune response, which may explain these successful long-term results treating Crohns fistulae with a high risk of recurrence, said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

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Trial Shows Stem Cells Provide Long-Term Relief from Dangerous Crohns Side Effect

Stem cell research has long been seen as a new frontier for disease therapeutics. By coaxing stem cells to form 3D miniature lung structures, University researchers are helping explain why.

In a collaborative study, University researchers devised a system to generate self-organizing human lung organoids, or artificially-grown organisms. These organoids are 3D models that can be used to better understand lung diseases.

Jason Spence, the assistant professor of internal medicine and cell and developmental biology, who was a senior author of the study, said one of the key implications of these lungs is the controlled environment they offer for future research.

These mini lungs will allow us to study diseases in a controlled environment and to develop and test new drugs, he said.

Specifically, Spence said, scientists will be able to take skin samples from patients with a particular form of a lung disease, reprogram the cells into stem cells and then generate lung tissue for further study. He said by analyzing the disease in a controlled environment, researchers can gain insight into the progression of various diseases and then tailor drugs for treatment.

Rackham student Briana Dye was also a lead author of the study. She said the team manipulated numerous signaling pathways involved with cell growth and organ formation to make the miniature lungs.

First, Dye said the scientists used proteins called growth factors to differentiate embryonic stem cells into endoderm, the germ layer that gives rise to the lungs. Different growth factors were then used to cause the endoderm to become lung tissue.

We add specific growth factors, proteins that turn on pathways in the cells, that will then cause them to lift off the monolayer so that we have this 3D spherical tissue, she said.

Previous research has used stem cells in a similar manner to generate brain, intestine, stomach and liver tissue. Dye said one of the advantages of stem cell research is its direct path to studying human tissue.

We have worked with many animal models in the past, Dye said. Animal models present obstacles because they dont exactly behave the way human tissue and cells do. This is why stem cells are so promising.

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Research develops mini-lung structures

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Newswise March 30, 2015 Two approaches to fat graftinginjection of fat cells versus fat-derived stem cellshave similar effects in reversing the cellular-level signs of aging skin, reports a study in the April issue of Plastic and Reconstructive Surgery, the official medical journal of the American Society of Plastic Surgeons (ASPS).

Since the facial rejuvenation results are the same, the simpler approach using fat cells plus the "stromal vascular fraction" has advantages over the more time-consuming stem cell fat technique. Dr. Gino Rigotti of Clinica San Francesco, Verona, Italy, directed a research team consisting of Luiz Charles-de-S and Natale Ferreira Gontijo-de-Amorim from Clinica Performa, Rio de Janeiro; and Andrea Sbarbati, Donatella Benati, and Paolo Bernardi from the Anatomy and Histology Institute, University of Verona.

Fat Grafts vs Stem Cells for Facial Rejuvenation The experimental study compared the two approaches to fat grafting for regeneration of the facial skin. In these procedures, a small amount of the patient's own fat is obtained by liposuction from another part of the body, such as the abdomen. After processing, the fat is grafted (transplanted) to the treated area, such as the face.

The study included six middle-aged patients who were candidates for facelift surgery. All underwent fat grafting to a small area in front of the ear.

One group of patients received fat-derived stem cells. Isolated and grown from the patients' fat, these specialized cells have the potential to develop into several different types of tissue. The other group underwent injection of fat cells along with the stromal vascular fraction (SVF)a rich mix of cell types, including stem cells.

Before and three months after fat grafting, samples of skin from the treated area were obtained for in-depth examination, including electron microscopy for ultrastructural-level detail.

After injection of fat cells plus SVF, the skin samples showed reduced degeneration of the skin's elastic fiber network, or "elastosis"a key characteristic of aging skin. These findings were confirmed by ultrastructural examination, which demonstrated the reabsorption of the elastosis and the development of relatively "young" elastic fibers.

In patients undergoing stem cell injection, the skin changes were essentially identical. "This result seems to suggest that the effect of a fat graft is, at least in part, due to its stem cell component," Dr Rigotti and coauthors write.

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Two Different Fat Graft Techniques Have Similar Effects on Facial Skin

Aminah Sagoe

Aminah Sagoe recently developed a skincare range called Emmaus. She opens up on why she set up the brand

Q: How did you delve into skincare treatment?

A: The inspiration came about while I was trying to treat my skin condition called keratosis pilaris, aka chicken skin. It is a common skin condition that causes rough patches and small, acne-like bumps, usually on the arms, thighs, cheeks and buttocks. The bumps are usually white, sometimes red, and generally do not hurt or itch. The condition can be frustrating because it is difficult to treat. In my quest to find a cure, I developed a skin care range to treat the condition. I have always been a product junkie.

Q: How long did this take?

A: It took 22 months of research to come up with these products. It has been very hectic but we kept going with the flow. It can be used by both sexes and it is the first natural skincare line in this part of the world to mix plant stem cells with natural ingredients. It can be used by people with eczema, psoriasis, scaly skin and uneven skin tone but it doesnt bleach. The ingredients are extremely healthy and safe for the skin. The three step range consists of the pampering smiling beads body wash, touch of love mini towels and a soothing softness bliss body lotion that nourishes and protects the skin

Q: What does Emmaus mean?

A: It is a biblical word and signifies a rebirth or a new beginning. I am a convert; I was born a Muslim but I am now a Christian. I got converted after I got married to my husband who is a Christian. I was in my late 20s when I picked up the Bible, read it and believed. Believing in Christ has brought me so much joy, peace and clarity.

Q: What are some of the challenges you faced while developing the products?

A: The formulation took so long to be formulated because it is made up of natural products and preservatives. At some point, we had issues where one product will interact with another and that took a lot of time to fix. The products do not bleach or alter your skin colour. The process took 15 months to complete.

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I dont have time for glamour Aminah Sagoe

Delray Beach, FL (PRWEB) March 27, 2015

Inspired by the latest advances in skin aging, BABORs Research and Innovation Center has developed a groundbreaking new skincare innovation: the anti-aging collection ReVersive, with the ultra-effective RE-YOUTH COMPLEX.

ReVersive is unique, as it contains a high-performance formula with four active ingredients that interact in perfect synergy. Designed as a complete anti-aging system, ReVersive restores youthful radiance and luminosity, leaving the complexion looking firmer and smoother with a beautifully even appearance.

VISIBLE EFFECTS FOR TIMELESSLY BEAUTIFUL SKIN

In a recent study conducted by the independent research organization, Derma Consult, the ReVersive collection showed impressive results. Testing was conducted on 100 women, aged 35 to 67, and in just 4 weeks time users reported the following exciting results:

99% MORE YOUTHFUL APPEARANCE 87% ENHANCED RADIANCE 90% FIRMER SKIN

THE RE-YOUTH COMPLEX

Telovitin: Keeps cells younger for longer Telovitin, an active ingredient based on Nobel Prize-winning research, combats skin aging at its source: cell activity. It protects the telomeres (the ends of the chromosomes) and thus extends the life cycle of the skin cells.

Agicyl: Activates defenses against skin aging This multifunctional active ingredient, which is extracted from the stem cells of the Alpine plant Globularia cordifolia, prevents the break down of the collagen fibers so that the skin retains its elasticity. It also neutralizes free radicals and environmental aggressors.

Lumicol: Creates luminosity and radiance The active radiance-boosting ingredient Lumicol, which is extracted from microalgae, can activate a protein that destroys these dark pigmentation and age spots to ensure an even-looking complexion and restore radiance.

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BABOR Launches Innovative Anti-Aging Collection ReVersive

Julie Gramyk 3 21 2015 Youtube
Julie Gramyk, Medical Esthetic, explains how Momentis #39; new skincare system is the first in the world to penetrate beyond the skin #39;s barrier and target the skin #39;s stem cells resulting in rebuilding...

By: judyrstak

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Julie Gramyk 3 21 2015 Youtube - Video

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Scientists at the University of Copenhagen have captured thousands of progenitor cells of the pancreas on video as they made decisions to divide and expand the organ or to specialize into the endocrine cells that regulate our blood sugar levels.

The study reveals that stem cells behave as people in a society, making individual choices but with enough interactions to bring them to their end-goal. The results could eventually lead to a better control over the production of insulin-producing endocrine cells for diabetes therapy.

The research is published in the scientific journal PLOS Biology.

Why one cell matters

In a joint collaboration between the University of Copenhagen and University of Cambridge, Professor Anne Grapin- Botton and a team of researchers including Assistant Professor Yung Hae Kim from DanStem Center focused on marking the progenitor cells of the embryonic pancreas, commonly referred to as 'mothers', and their 'daughters' in different fluorescent colours and then captured them on video to analyse how they make decisions.

Prior to this work, there were methods to predict how specific types of pancreas cells would evolve as the embryo develops. However, by looking at individual cells, the scientists found that even within one group of cells presumed to be of the same type, some will divide many times to make the organ bigger while others will become specialized and will stop dividing.

The scientists witnessed interesting occurrences where the 'mother' of two 'daughters' made a decision and passed it on to the two 'daughters' who then acquired their specialization in synchrony. By observing enough cells, they were able to extract logic rules of decision-making, and with the help of Pau Ru, a mathematician from the University of Cambridge, they developed a mathematical model to make long-term predictions over multiple generations of cells.

Stem cell movies

'It is the first time we have made movies of a quality that is high enough to follow thousands of individual cells in this organ, for periods of time that are long enough for us to follow the slow decision process. The task seemed daunting and technically challenging, but fascinating", says Professor Grapin-Botton.

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Stem cells make similar decisions to humans

Researchers at the University of Cambridge have grown functional "mini-lungs" using stems cells derived from the skin cells of patients with a debilitating lung disease. Not only can the development help them in coming up with effective treatments for specific lung diseases like cystic fibrosis, but the process has the potential to be scaled up to screen thousands of new compounds to identify potential new drugs.

Creating miniature organoids has been the focus of many a research group, as it allows scientists to better understand the processes that take place inside an organ, figure out how specific diseases occur and develop or even work towards creating bioengineered lungs.

The research team from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute studied a lung disease called cystic fibrosis, which is caused by genetic mutation and shortens a patient's average lifespan. Patients have great difficulty breathing as the lungs are overwhelmed by thickened mucus.

To create working mini-lungs, the researchers took skin cells from patients with the most common form of cystic fibrosis and reprogrammed them to an induced pluripotent state (iPS), which allows the cells to grow into a different type of cell inside the body.

They then activated a process called gastrulation which pushes the cells to form distinct layers such as the endoderm and foregut. The cells were then pushed further to form distal airway tissue, the part of the lung that deals with exchange of gases.

In a sense, what weve created are mini-lungs," says Dr Nick Hannan, the lead researcher. 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."

To find out whether the mini lungs could actually be used to screen drugs, the team tested them out with the aid of chloride-sensitive fluorescent dye. Cells from cystic fibrosis patients typically malfunction and don't allow the chloride to pass through, so there's no change in fluorescence levels.

The team added a molecule that's currently undergoing clinical trials and noted a change in fluorescence, signaling that it was effective in getting the diseased lung cells to function properly and that the mini lungs could, in principle, be used to test potential new drugs.

"Were 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," says 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."

The research was published in the journal Stem Cells and Development.

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Scientists create functioning "mini-lungs" to study 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."

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Scientists grow 'mini-lungs' to aid study of cystic fibrosis

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.

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

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 Wednesday (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 contain histones, DNA-packaging proteins, 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 super-enhancers, 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, called an epicenter, where all the stem cell transcription factors bind, and they linked it to a gene that glowed 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 appeared 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 that can initiate such dramatic changes in gene expression.

"Importantly, we link this pioneer factor to super-enhancer dynamics, giving these domains a 'one-two punch' in governing cell identity. In the case of stem cell plasticity, Sox9 appears to be the lead factor that activates the super-enhancers that amplify genes associated with stemness," Fuchs says. "These discoveries offer new insights into the way in which stem cells choose their fates and maintain plasticity while in transitional states, such as in culture or when repairing wounds."

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

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."

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

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Cambridge stem cell scientists searching for new cystic fibrosis treatments have grown "mini-lungs" in a laboratory.

The millimetre-wide cell clusters were created using stem cells derived from the skin of patients with the devastating lung disease.

They are the latest in a line of 3D "organoids" produced to mimic the behaviour of specific body tissues, following "mini-brains" for studying Alzheimer's disease and "mini-livers" to model diseases of the liver.

Dr Nick Hannan, led the team from Cambridge University.

He said: "In a sense, what we've created are 'mini-lungs'.

"While they only represent the distal (outer) 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."

Cystic fibrosis occurs when the movement of water to the inside of the lungs is reduced, causing a build up of thick mucus that leads to a high risk of infection.

The scientists reprogrammed ordinary skin cells to create stem cells that could be transformed into lung tissue.

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Stem cell "mini-lungs" created in Cambridge University lab

(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

Experiments placed Sox9 at the crux of a shift in gene expression associated with hair follicle stem cell identity

IMAGE:Researchers made stem cells fluoresce green (at the base of hair follicles above) by labeling their super-enhancers, regions of the genome bound by gene-amplifying proteins. It appears one such protein,... view more

Credit: Laboratory of Mammalian Cell Biology and Development at The Rockefeller University/Nature

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 Wednesday (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 contain histones, DNA-packaging proteins, 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 super-enhancers, 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, called an epicenter, where all the stem cell transcription factors bind, and they linked it to a gene that glowed 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 appeared in culture, but not in skin. When they wounded the skin, then the green glow switched on.

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Scientists pinpoint molecule that switches on stem cell genes

Stem cells are special cells that can turn into any kind of cells in the body. They serve as a repair system for the body. There are two main types of human stem cells: embryonic stem cells and adult stem cells.

Embryonic stem cells are cells that come from an unborn baby (embryo). Those are NOT the cells that are used for this product.LUMINESCEformulation uses technology derived from the study of Adult Stem Cells.

Stem cells communicate with tissue cells to induce repair. They produce many different growth factors and "communication" chemicals to do this.Dr Nathan Newmanhas been able to take stem cells in the lab, and separate them from the solution that holds the growth factors. This media is the foundation of theLUMINESCEproduct.

What is the relationship between growth factors and the stem cell technology?

The patent-pending technology ofLUMINESCEprovides for the delivery of key growth factors found in natural skin. As we age, the production of these growth factors within skin is reduced, and leads to wrinkling and thinning of the skin. By re-introducing these factors through the daily application ofLUMINESCE, damaged skin cells may be repaired, and skin tissue re-generated.

Stem cells are cells that have the ability to grow into any kind of cell in the body, and they rely on special signals to tell them what cells they will ultimately become. If you know the stem cell language, then you could communicate to the cells.

In this way, you could have stem cells that become new young skin cells, rebuild collagen, and deliver a new younger looking skin.

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Stem Cells, Skin Care and Dr Newman | Skin Care