Category Archives: Stem Cells

Online tutorial on Embryonic stem cells - Biology
Expertsmind:- Embryonic stem cells ES cells are pluripotent stem cells derived from inner cell mass of a blastocyst, an early-stage preimplantation embryo. Human embryos reach the blastocyst...

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Online tutorial on Embryonic stem cells - Biology - Video

Brazilian researchers at D'OR Institute for Research and Education (IDOR) and Federal University of Rio de Janeiro (UFRJ) have taken what they describe as an important step toward using the implantation of stem cell-generated neurons as a treatment for Parkinson's disease. Using an FDA approved substance for treating stomach cancer, Rehen and colleagues were able to grow dopamine-producing neurons derived from embryonic stem cells that remained healthy and functional for as long as 15 months after implantation into mice, restoring motor function without forming tumors.

Parkinson's, which affect as many 10 million people in the world, is caused by a depletion of dopamine-producing neurons in the brain. Current treatments include medications and electrical implants in the brain which causes severe adverse effects over time and fail to prevent disease progression. Several studies have indicated that the transplantation of embryonic stem cells improves motor functions in animal models. However, until now, the procedure has shown to be unsafe, because of the risk of tumors upon transplantation.

To address this issue, the researchers tested for the first time to pre-treat undifferentiated mouse embryonic stem cells with mitomycin C, a drug already prescribed to treat cancer. The substance blocks the DNA replication and prevents the cells to multiply out of control.

The researchers used mice modeled for Parkinson's. The animals were separated in three groups. The first one, the control group, did not receive the stem cell implant. The second one, received the implant of stem cells which were not treated with mitomycin C and the third one received the mitomycin C treated cells.

After the injection of 50,000 untreated stem cells, the animals of the second group showed improvement in motor functions but all of them died between 3 and 7 weeks later. These animals also developed intracerebral tumors. In contrast, animals receiving the treated stem cells showed improvement of Parkinson's symptoms and survived until the end of the observation period of 12 weeks post-transplant with no tumors detected. Four of these mice were monitored for as long as 15 months with no signs of pathology.

Furthermore, the scientists have also shown that treating the stem cells with mitomycin C induced a four-fold increase in the release of dopamine after in vitro differentiation.

"This simple strategy of shortly exposing pluripotent stem cells to an anti-cancer drug turned the transplant safer, by eliminating the risk of tumor formation," says the leader of the study Stevens Rehen, Professor at UFRJ and researcher at IDOR.

The discovery, reported on April in the journal Frontiers in Cellular Neuroscience, could pave the way for researchers and physicians to propose a clinical trial using pluripotent stem cells treated with mitomycin C prior to transplant to treat Parkinson's patients and also other neurodegenerative conditions.

"Our technique with mitomycin C may speed the proposal of clinical trials with pluripotent cells to several human diseases," says Rehen. "It is the first step to make this kind of treatment with stem cells possible."

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Possible progress against Parkinson's and good news for stem cell therapies

CAMBRIDGE, Mass. (April 2, 2015) - A team of Whitehead Institute scientists has discovered that during division, stem cells distinguish between old and young mitochondria and allocate them disproportionately between daughter cells. As a result, the daughter cell destined to remain a stem cell receives predominantly young mitochondria, while the cell meant to differentiate into another cell type carries with it a higher compliment of the aged organelles.

This asymmetric apportioning of cellular contents may represent a mechanism through which stem cells prevent the accumulation of damage in their lineage over time.

"There is a fitness advantage to renewing your mitochondria," says Whitehead Member David Sabatini, whose lab reports on the phenomenon online this week in the journal Science. "Stem cells know this and have figured out a way to discard their older components."

Among the hallmarks of stem cells is so-called asymmetric cell division. Unlike their ordinary cellular counterparts, which divide symmetrically to create two cells with identical fates, stem cell division can produce one daughter cell that will remain a stem cell and another bound for further differentiation into another cell type. Scientists have observed that non-mammalian organisms are able to apportion damaged components asymmetrically during cell division, but it was unclear whether mammalian stem cells could behave similarly.

To answer this question, scientists in Sabatini's lab studied stem-like cells (SLCs) from cultures of immortalized human mammary epithelial cells. These SLCs were chosen because they express genes associated with the stem-cell state (referred to as stemness), are able to form structures known as mammospheres in culture. To track the destinations of subcellular components during cell division, the researchers, led by former postdoctoral scientist Pekka Katajisto, tagged the components--including lysosomes, mitochondria, Golgi apparatus, ribosomes, and chromatin--with a fluorescent protein that glows when hit by a pulse of ultraviolet light.

By tracing the movements of the glowing organelles, the researchers were able to demonstrate that while the normal epithelial cells distributed all of the tagged components symmetrically to daughter cells, the SLCs localized their older mitochondria distinctly and passed on the lion's share of them to the daughter cells headed for differentiation. The researchers ultimately found that the number of older mitochondria in those cells was roughly six times that in daughter cells whose fate was to remain as stem cells.

In a series of additional experiments, the scientists found that cells that inherited fewer old mitochondria during asymmetric division formed three times the number of mammospheres per 1000 cells than the daughter cells inheriting a greater proportion old mitochondria. This was an indication that cells with fewer of these old organelles were, by the mammosphere-forming criterion, more stem-like. Further, they discovered that chemically disrupting the cells' inherent mitochondrial quality-control mechanisms prevented asymmetric apportioning of young and old mitochondria and caused the loss of stem-like characteristics. Taken together, these results indicate that this disproportionate allocation of aged mitochondria during stem cell division is essential for maintaining stemness in the next generation.

"While we do not know how stem cells recognize the age of their mitochondria, forced symmetric apportioning of aged mitochondria resulted in loss of stemness in all of the daughter cells," says Katajisto, the first author of the Science paper who now runs a lab at the Institute of Biotechnology at University of Helsinki. "This suggests that the age-selective apportioning of old and potentially damaged organelles may be a way to fight stem cell exhaustion and aging."

Katajisto is now exploring whether this phenomenon occurs in other cell types beyond the human mammary epithelial SLCs examined here as well as in in vivo studies.

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Age-discrimination during cell division maintains the 'stem' in stem cells

IMAGE:Human mammary stem-like cell apportions aged mitochondria asymmetrically between daughter cells. Mitochondria were labeled age-selectively red 51 hours prior to imaging, leaving mitochondria that are younger unlabelled. The daughter cell... view more

Credit: Julia Dhla

Tissue stem cells, that continuously renew our tissues, can divide asymmetrically to produce two types of daughter cells. One will be the new stem cell, where as the other will give rise to the differentiating cells of the tissue.

A study jointly lead by laboratories in the Institute of Biotechnology and Massachusetts Institute of Technology (MIT) investigated whether stem cells may also use asymmetric cell division to reduce accumulation of cellular damage. Damage buildup can cause stem cell exhaustion that results in reduced tissue renewal and aging.

Researchers developed a novel approach to follow cellular components, such as organelles, age-selectively during cell division.

"We found that stem cells segregate their old mitochondria to the daughter cell that will differentiate, whereas the new stem cell will receive only young mitochondria" says Pekka Katajisto, a Group leader and Academy research fellow at BI.

Mitochondria appear to be particularly important for stem cells, as other analyzed organelles were not similarly age-discriminated, and since inhibition of normal mitochondrial quality control pathways stopped their age-selective segregation.

"There is a fitness advantage to renewing your mitochondria," says David Sabatini, Professor at MIT and Whitehead Institute. "Stem cells know this and have figured out a way to discard their older components."

While the mechanism used by stem cells to recognize the age of their mitochondria remains unknown, forced symmetric apportioning of aged mitochondria resulted in loss of stemness in all of the daughter cells. "This suggests that the age-selective apportioning of old and potentially damaged organelles may be a way to fight stem cell exhaustion and aging," says Katajisto.

Katajisto laboratory is now exploring how old mitochondria differ from old, and whether this phenomenon occurs in other cell types beyond the human mammary stem-like cells examined here as well as in in vivo.

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Stem cells age-discriminate organelles to maintain stemness

According to the Christopher and Dana Reeve Foundation, nearly one in 50 people are living with paralysis.

Until now, there wasn't much hope.

But, a new study involving stem cells has doctors and patients excited.

Two years ago, Brenda Guerra's life changed forever.

"They told me that I went into a ditch and was ejected out of the vehicle," says Brenda.

The accident left the 26-year-old paralyzed from the waist down and confined to a wheelchair.

"I don't feel any of my lower body at all," says Brenda.

Brenda has traveled from Kansas to UC San Diego to be the first patient to participate in a ground-breaking safety trial, testing stem cells for paralysis.

"We are directly injecting the stem cells into the spine," says Dr. Joseph Ciacci, a neurosurgeon at UC San Diego.

The stem cells come from fetal spinal cords. The idea is when they're transplanted they will develop into new neurons and bridge the gap created by the injury by replacing severed or lost nerve connections. They did that in animals and doctors are hoping for similar results in humans. The ultimate goal: to help people like Brenda walk again.

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Stem cell procedures for paralysis patients

A new study has identified an enzyme in mesenchymal stem cells (MSCs) that is responsible for creating either bone or fat a finding that scientists argue may lay the groundwork for new osteoporosis and obesity treatments.

Researchers at the Interdisciplinary Stem Cell Institute (ISCI), at the University of Miami Miller School of Medicine, say their findings are preliminary but promising.

We got very interested in the idea of there are all of these diseases of the bone that plague human beings, so we wondered if we understood the cells better, would we able to understand their role in diseases, lead study author Dr. Joshua Hare, founding director of ISCI, told FoxNews.com.

The study was conducted using mice that lacked an enzyme that regulates the level of nitric oxide signaling, a key in determining whether MSCs become fat or bone cells. MSCs from the mice that genetically lacked the enzyme made more bone cells and fewer fat cells. The researchers identified the switch, called a GSNOR, which they believe will translate clinically to help better understand how drugs may be able to manipulate the GSNOR, possibly offering future treatment for obesity and bone-disease related illnesses.

Drugs do exist to block the GSNOR. We do plan to do tests using the drug in actual circumstances of osteoporosis and study them at a very biochemical level, Hare said.

But the switch was not without consequence, as it also triggered a harmful side effect. When the animal started to produce more bone, it also turned on a pathway that created other cells to eat some of the bone, so we havent perfected the way that this would be used clinically, Hare said.

Hare said that once the potential therapy is perfected, it could have a profound effect on the aging populations quality of life.

By providing a way to produce more bone cells, MSCs create the potential to keep people active for much longer than previously possible and thus improve overall quality of life for seniors, he said.

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Study finds stem cells can be manipulated to promote bone growth

Two approaches to fat grafting -- injection of fat cells versus fat-derived stem cells -- have 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.

The researchers also found "suggestive" evidence that the rejuvenating effects of fat grafting are related to new formation of microscopic blood vessels. Further studies are needed to confirm this hypothesis, however. Dr. Rigotti comments, "In any case, this is the first study presenting clinical evidence showing skin rejuvenation after fat grafting and highlighting the anatomical and structural changes that are the basis of this rejuvenation."

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Two different fat graft techniques have similar effects on facial skin

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

SALT LAKE CITY, Utah. (Ivanhoe Newswire) -- Multiple sclerosis is a scary and unpredictable disease. A patient's own immune system attacks the nervous system, causing numbness, dizziness, and in some cases, paralysis. But a team of researchers at the University of Utah found that human stem cells didn't just stop symptoms in animals, they reversed them.

Rachel Taylor was diagnosed with MS 14 years ago.

It was terrifying. It was like having a wet, heavy blanket put over your life. I was active, I was a runner, I was outdoors playing and over the course of a few months, I couldn't figure out why I couldn't keep up Taylor told Ivanhoe.

Rachel knew what was wrong; she'd been working with the MS society bike rides for years. Rachel's in remission now, but she is still thrilled with Tom Lane Ph.D., Professor of Pathology at the University of Utah's stem cell discovery.

Professor Lane told Ivanhoe, We have animals that are paralyzed that cannot right themselves, and once we engraft the neural stem cells into the spinal cords, within three weeks, the majority of the animals, about 80 to 85 percent, will regain motor skills.

Researchers say MS damages myelin, a layer around nerve cells. Once injected, the human neural cells stimulate the mouse's own cells to repair the damage. When nerve cell function returns, the mice can walk and run again.

Rachel says this discovery could be life-changing for many of her friends.

Researchers say after the mice regained function, their bodies rejected the stem cells, which vanished, eliminating the possibility that those cells could become tumors. Professor Lane is hoping this procedure could be ready for human clinical trials in two to three years.

Contributors to this news report include: Cyndy McGrath, Supervising Producer; Wendy Chioji, Field Producer; Cortni Spearman, Assistant Producer; Jason Ball, Videographer and Jamison Koczan, Editor.

BACKGROUND: Over the past 50 years, it has been discovered that more than two to three times as many women develop Multiple Sclerosis than men. Although there is no evidence that MS is directly inherited, genetic risk factors have been studied and were found to increase the possibility of developing the disease. Low vitamin D and smoking are considered environmental factors that can increase the risk of MS. Symptoms of MS occur when there is inflammation in the central nervous system inflammation which, in turn, damages the protective insulation of nerve fibers (myelin), the cells that make the myelin (oligodendrocytes) and sometimes the actual nerve fiber. MS does not always cause paralysis, and about two-thirds of people with MS are still able to walk, usually with the help of an aid (cane, crutches). (Source: http://www.nationalmssociety.org/What-is-MS, http://www.nationalmssociety.org/What-is-MS/MS-FAQ-s#question-Who-gets-MS)

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Stem cells reverse MS: Medicine's next big thing?

Lung diseases like emphysema and pulmonary fibrosis are common among people with malfunctioning telomeres, the "caps" or ends of chromosomes. Now, researchers from Johns Hopkins say they have discovered what goes wrong and why.

Mary Armanios, M.D., an associate professor of oncology at the Johns Hopkins University School of Medicine., and her colleagues report that some stem cells vital to lung cell oxygenation undergo premature aging -- and stop dividing and proliferating -- when their telomeres are defective. The stem cells are those in the alveoli, the tiny air exchange sacs where blood takes up oxygen.

In studies of these isolated stem cells and in mice, Armanios' team discovered that dormant or senescent stem cells send out signals that recruit immune molecules to the lungs and cause the severe inflammation that is also a hallmark of emphysema and related lung diseases.

Until now, Armanios says, researchers and clinicians have thought that "inflammation alone is what drives these lung diseases and have based therapy on anti-inflammatory drugs for the last 30 years."

But the new discoveries, reported March 30 in Proceedings of the National Academy of Sciences, suggest instead that "if it's premature aging of the stem cells driving this, nothing will really get better if you don't fix that problem," Armanios says.

Acknowledging that there are no current ways to treat or replace damaged lung stem cells, Armanios says that knowing the source of the problem can redirect research efforts. "It's a new challenge that begins with the questions of whether we take on the effort to fix this defect in the cells, or try to replace the cells," she adds.

Armanios and her team say their study also found that this telomere-driven defect leaves mice extremely vulnerable to anticancer drugs like bleomycin or busulfan that are toxic to the lungs. The drugs and infectious agents like viruses kill off the cells that line the lung's air sacs. In cases of telomere dysfunction, Armanios explains, the lung stem cells can't divide and replenish these destroyed cells.

When the researchers gave these drugs to 11 mice with the lung stem cell defect, all became severely ill and died within a month.

This finding could shed light on why "sometimes people with short telomeres may have no signs of pulmonary disease whatsoever, but when they're exposed to an acute infection or to certain drugs, they develop respiratory failure," says Armanios. "We don't think anyone has ever before linked this phenomenon to stem cell failure or senescence."

In their study, the researchers genetically engineered mice to have a telomere defect that impaired the telomeres in just the lung stem cells in the alveolar epithelium, the layer of cells that lines the air sacs. "In bone marrow or other compartments, when stem cells have short telomeres, or when they age, they just die out," Armanios says. "But we found that instead, these alveolar cells just linger in the senescent stage."

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Premature aging of stem cell telomeres, not inflammation, linked to emphysema