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How a Silly Putty ingredient could advance stem cell therapies

14 hours ago University of Michigan researchers have found that mechanical forces in the environment of human embryonic stem cells influences how they differentiate, or morph into the body's different cell types. To arrive at the findings, they cultured the stem cells on ultrafine carpets made of microscopic posts of a key ingredient in Silly Putty. Credit: Ye Tao, Rose Anderson, Yubing Sun, and Jianping Fu.

The sponginess of the environment where human embryonic stem cells are growing affects the type of specialized cells they eventually become, a University of Michigan study shows.

The researchers coaxed human embryonic stem cells to turn into working spinal cord cells more efficiently by growing the cells on a soft, utrafine carpet made of a key ingredient in Silly Putty. Their study is published online at Nature Materials on April 13.

This research is the first to directly link physical, as opposed to chemical, signals to human embryonic stem cell differentiation. Differentiation is the process of the source cells morphing into the body's more than 200 cell types that become muscle, bone, nerves and organs, for example.

Jianping Fu, U-M assistant professor of mechanical engineering, says the findings raise the possibility of a more efficient way to guide stem cells to differentiate and potentially provide therapies for diseases such as amyotrophic lateral sclerosis (Lou Gehrig's disease), Huntington's or Alzheimer's.

In the specially engineered growth systemthe 'carpets' Fu and his colleagues designedmicroscopic posts of the Silly Putty component polydimethylsiloxane serve as the threads. By varying the post height, the researchers can adjust the stiffness of the surface they grow cells on. Shorter posts are more rigidlike an industrial carpet. Taller ones are softermore plush.

The team found that stem cells they grew on the tall, softer micropost carpets turned into nerve cells much faster and more often than those they grew on the stiffer surfaces. After 23 days, the colonies of spinal cord cellsmotor neurons that control how muscles movethat grew on the softer micropost carpets were four times more pure and 10 times larger than those growing on either traditional plates or rigid carpets.

"This is extremely exciting," Fu said. "To realize promising clinical applications of human embryonic stem cells, we need a better culture system that can reliably produce more target cells that function well. Our approach is a big step in that direction, by using synthetic microengineered surfaces to control mechanical environmental signals."

Fu is collaborating with doctors at the U-M Medical School. Eva Feldman, the Russell N. DeJong Professor of Neurology, studies amyotrophic lateral sclerosis, or ALS. It paralyzes patients as it kills motor neurons in the brain and spinal cord.

Researchers like Feldman believe stem cell therapiesboth from embryonic and adult varietiesmight help patients grow new nerve cells. She's using Fu's technique to try to make fresh neurons from patients' own cells. At this point, they're examining how and whether the process could work, and they hope to try it in humans in the future.

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How a Silly Putty ingredient could advance stem cell therapies

StemCell Doctors

by Tracy Smith

Technically, Vitamin D is not a true vitamin because, under the right circumstances, the body can synthesize its own using sunlight and cholesterol. It s really a steroid hormone that strongly affects gene expression and resistance to multiple diseases. It s vitally necessary for life and health, and new discoveries show that it s more important for vibrant, youthful health than we ever thought before. Vitamin D deficiency is chronic around the world, even in developed countries. It s estimated that the incidence of many cancers could be cut in half if we all got enough of this important nutrient. (ILLUSTRATION: Vitamin D3 is often available in gel caplet form.)

Humans and, in fact, most mammals create their own Vitamin D when exposed to direct sunlight. But, because excessive exposure to the Sun is known to increase the risk of skin cancer, doctors generally don t recommend being out in the sunlight as a way to get adequate Vitamin D. Instead, supplements are called for.

Vitamin D, in its D3 form known to chemists as cholecalciferol (don t worry, I won t force you to pronounce it!), is absolutely necessary for health. It was first discovered over a century ago when doctors were trying to find a cure for rickets, a serious bone disease that often affects children. It was noticed that this disease started to become much more common during the Industrial Revolution, when large numbers of people moved from the countryside and outdoors work to polluted cities where they worked in dark, dingy factories. Scientists also found that those living in warm, sunny places were much less likely to contract rickets than those living in cloudy, northern, high-latitude climates. Eventually it was discovered that Sun exposure or the taking of cod liver oil could absolutely prevent the disease, proving it to be a deficiency disease, meaning that it is not caused by a virus or other microorganism, but by a simple lack of something essential in the victim s diet. That something proved to be Vitamin D.

Vitamin D deficiency is very common. A study in France showed that fully 14 percent of otherwise healthy adults had extremely low levels of Vitamin D. Another study, this one of medical professionals living in New England, indicated that 42 percent of them had a Vitamin D deficiency by the end of Winter among those who did not take D3 supplements. But among those who did supplement their diet with D3, the deficiency rate was only 11 percent!

It s pretty clear that without enough of this vitamin, you can get very sick indeed. And it s also clear that many of us, in fact, aren t getting enough. But there s a lot more to Vitamin D3 than preventing rickets. The vitamin has anti-aging and anti-inflammatory aspects, and it has been shown to positively affect your mental outlook, too, helping to combat depression. Vitamin D3 can even help improve the lifespan and survival of the neurons which make up your brain and nervous system. Let s take a look at what it can do for you!

One of the major problems faced by older women is osteoporosis, which greatly increases the risk of bone fractures and hip fractures late in life can sometimes amount to a death sentence. In a study commissioned by the Women s Health Initiative, it was found that women on a Vitamin D3 and calcium carbonate supplementation program had 12 percent fewer hip fractures that women taking a placebo. These effects were seen on fairly high doses of D3 over 800 IU per day.

Vitamin D3 boosts your immune system and your body s ability to fight off all kinds of diseases. Immune system cells have structures with Vitamin D receptors, and it s been shown that being deficient in this vitamin increases your risk of of infection generally and especially increases your risk of autoimmune diseases.

Vitamin D3 helps your body fight off viral respiratory infections.

Vitamin D3 also has been shown to be beneficial in helping your body fight off the flu.

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StemCell Doctors

Center denies hand in Ateneo alum's death, calls for probe into all hospitals and docs she consulted

By: InterAksyon.com April 12, 2014 12:57 PM

InterAksyon.com The online news portal of TV5

The Green and Young Health and Wellness Center, the facility at the center of allegations of malpractice that allegedly led to the death of an Ateneo de Manila alumna in 2013, on Saturday called for a broader investigation into "all hospitals where she was admitted and all doctors who treated her right before she died".

Stressing that the student, Katherine Grace Tan, "was never given stem cell treatment by the Center or Dr. Antonia Park," the Green and Yough Health and Wellness Center said it was unjustly singled out and wrongly portrayed as accountable for the young womans death.

A cum laude graduate from the Ateneo de Manila University, Tan was reported to be suffering from Hodgkin's lymphoma, when she allegedly underwent treatment at Parks wellness center.

The girl's father, Bernard Tan, claimed his daughter underwent stem cell therapy there after allegedly being advised by Park.

In a statement, however, the Green and Young Health and Wellness Center in Tagaytay City said: "Ms. Katherine Grace Tan was never given stem cell treatment by the Center or Dr. Antonia Park. The allegation is not true."

The Center's statement, released through its lawyer, Stephen Cascolan, added: "As to the cause of death, Ms. Tan's memory deserves to be honored in a manner that is true, fair, and just. Mr. Bernard Tan, the father who brought his daughter to many other physicians right before Ms. Tan died, and long after she visited the Center in July 2012, should show to the public the competent and actual medical findings showing cause of death. All hospitals where she was admitted and all doctors who treated her right before she died should be investigated. An autopsy be conducted to ascertain real and actual cause of death. Only in this manner can the issue be resolved."

Not licensed in the Philippines

Earlier this month, it was reported that Park hadadmitted that she wasn't licensed to practice in the Philippines. Records from the theProfessional Regulatory Commission as of August 2013 showed that Park was not on the list of physicians authorized to practice medicine in the country.

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Center denies hand in Ateneo alum's death, calls for probe into all hospitals and docs she consulted

Grateful patient donates $6.5M to Shiley Eye Center

Doctors perform eye surgery in an operating room at Shiley Eye Center Wednesday. The center recently received a $6.5 million gift to help establish a new stem cell research laboratory.

A $6.5 million donation from an unnamed patient will help the Shiley Eye Center at UC San Diego strengthen its focus on stem cells, which hold the promise of repairing damage done by diseases such as glaucoma and macular degeneration.

Dr. Robert Weinreb, the centers director and a widely-published glaucoma researcher, said hes conducting a worldwide search for stem cell scientists to come to Shiley, which last year ranked fourth in National Institutes of Health funding among ophthalmology research centers nationwide.

Stem cells are known for their ability to transform themselves into nearly any other type of cell in the body, and scientists are exploring ways to use this Rosetta stone of biology to repair damage caused by cancer, diabetes and a range of other diseases.

Theres also huge potential for stem cells and the human eye.

Were going to use the stem cells to treat retinal diseases including macular degeneration, to rescue the optic nerve in glaucoma, as well as to replace the diseased layers of the cornea in patients with blinding corneal diseases, Weinreb said.

Vision loss is a growing problem as more and more baby boomers reach retirement age.

Paul Kelly, 83, undergoes a test that measures the curvature of his corneas Wednesday at Shiley Eye Center in La Jolla.

The U.S. Centers for Disease Control and Prevention said about 1.8 million Americans have advanced age-related macular degeneration and projects that number to soar to 2.9 million by 2020. In addition, the incidence of glaucoma and diabetic retinopathy is expected to grow significantly in the same time frame.

But theres hope.

Continued here:
Grateful patient donates $6.5M to Shiley Eye Center

Grateful patient donates $6.5 million to Shiley Eye Center

Doctors perform eye surgery in an operating room at Shiley Eye Center Wednesday. The center recently received a $6.5 million gift to help establish a new stem cell research laboratory.

A $6.5 million donation from an unnamed patient will help the Shiley Eye Center at UC San Diego strengthen its focus on stem cells, which hold the promise of repairing damage done by diseases such as glaucoma and macular degeneration.

Dr. Robert Weinreb, the centers director and a widely-published glaucoma researcher, said hes conducting a worldwide search for stem cell scientists to come to Shiley, which last year ranked fourth in National Institutes of Health funding among ophthalmology research centers nationwide.

Stem cells are known for their ability to transform themselves into nearly any other type of cell in the body, and scientists are exploring ways to use this Rosetta stone of biology to repair damage caused by cancer, diabetes and a range of other diseases.

Theres also huge potential for stem cells and the human eye.

Were going to use the stem cells to treat retinal diseases including macular degeneration, to rescue the optic nerve in glaucoma, as well as to replace the diseased layers of the cornea in patients with blinding corneal diseases, Weinreb said.

Vision loss is a growing problem as more and more baby boomers reach retirement age.

Paul Kelly, 83, undergoes a test that measures the curvature of his corneas Wednesday at Shiley Eye Center in La Jolla.

The U.S. Centers for Disease Control and Prevention said about 1.8 million Americans have advanced age-related macular degeneration and projects that number to soar to 2.9 million by 2020. In addition, the incidence of glaucoma and diabetic retinopathy is expected to grow significantly in the same time frame.

But theres hope.

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Grateful patient donates $6.5 million to Shiley Eye Center

New Technology 'Grows' Man-Made Body Parts

Man-made (or lab-grown) organs have gone from science fiction to fact in recent years. While lab-grown ears have become famous thanks to the striking picture of a mouse with an ear grown on its back, recent technology, including 3-D printing and stem cell use, has meant more complex organs are being made by scientists.

Everything from ears to tracheas and, most recently, vaginas has been recreated in a lab setting. But doctors have also refined old-fashioned surgical techniques to give patients who have been disfigured a second nose or even a face through operations.

To show just how far this seemingly fantastical medicine has come, weve found a few of the most impressive man-made body parts.

See More Medical Marvels

A study published this week in the Lancet Medical Journal revealed how researchers were able to grow vaginas in a laboratory setting.

Researchers from Wake Forest University School of Medicine in Winston-Salem, N.C., and Metropolitan Autonomous University in Mexico City took tissue samples from four adolescent female patients from Mexico between the ages of 13 and 18, and then were able to construct vaginal components by culturing and expanding tissues in special incubators.

The patients, who were born with incomplete vaginas because of a genetic disorder, then underwent surgery and had the vaginal tissue implanted. In the years following the surgery, the patients reported normal sexual function.

In China, doctors were able to regrow a mans nose. The twist is that they had to temporarily put the nose on the mans forehead.

The patient identified as Xiaolian, according to Reuters, had an infection that left his nose damaged and disfigured.

To help him, doctors used tissue expanders and reshaped a second nose over a period of months on Xiaolians forehead. Eventually, when surgery is performed, theyll use cartilage from his rib to help strengthen his nose.

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New Technology 'Grows' Man-Made Body Parts

Researchers identify transcription factors distinguishing glioblastoma stem cells

PUBLIC RELEASE DATE:

10-Apr-2014

Contact: Sue McGreevey smcgreevey@partners.org 617-724-2764 Massachusetts General Hospital

The activity of four transcription factors proteins that regulate the expression of other genes appears to distinguish the small proportion of glioblastoma cells responsible for the aggressiveness and treatment resistance of the deadly brain tumor. The findings by a team of Massachusetts General Hospital (MGH) investigators, which will be published in the April 24 issue of Cell and are receiving advance online release, support the importance of epigenetics processes controlling whether or not genes are expressed in cancer pathology and identify molecular circuits that may be targeted by new therapeutic approaches.

"We have identified a code of 'molecular switches' that control a very aggressive subpopulation of brain cancer cells, so-called glioblastoma stem cells," says Mario Suv, MD, PhD, of the MGH Department of Pathology and Center for Cancer Research, co-lead author of the Cell article. "Understanding what drives these aggressive cells will give us insights into alternative ways of eliminating them and potentially changing the course of this very deadly tumor."

Normal biological development follows an orderly hierarchical progression from stem cells, capable of differentiating into almost any type of cell, to progenitor cells, giving rise to specific subtypes of cells and tissues, to fully differentiated cells. While the process usually proceeds in a one-way direction, artificially inducing the activity of key transcription factors can reprogram differentiated cells back into a stem-like state, a discovery honored with the 2012 Nobel prize.

Small populations of adult stem cells with somewhat limited developmental potential are responsible for the body's ability to heal injuries and replace worn out cells and tissues, and evidence is growing that rare cancer stem cells are responsible for the uncontrolled growth of some malignant tumors, including glioblastoma. Several studies have used cell-surface markers proteins found on the outer membranes of tumor cells to identify glioblastoma stem cells; but the specific markers used have been controversial and cannot reflect molecular processes going on within tumor cells. The current study was designed to clarify the cellular hierarchy underlying glioblastoma, to identify epigenetic factors that distinguish glioblastoma stem cells from more differentiated tumor cells and to suggest potential therapies targeting those factors.

In a series of experiments, the researchers first identified a set of 19 transcription factors that were expressed at significantly greater levels in cultured human glioblastoma stem cells capable of tumor propagation than in differentiated tumor cells. Testing each of these factors for their ability to return differentiated tumor cells to a stem-like state, identified a combination of four POU3F2, SOX2, SALL2 and OLIG2 that was able to reprogram differentiated tumor cells back into glioblastoma stem cells, both in vitro and in an animal model.

The investigators then confirmed that these four factors and their corresponding regulatory elements the DNA segments to which transcription factors bind were active in from 2 to 7 percent of human glioblastoma cells, cells that also expressed a known stem cell marker. They also showed that inhibiting the action of an important regulatory protein complex that involves a known target gene of one of the core transcription factors a gene active in stem-like glioblastoma cells but not differentiated cells caused glioblastoma stem cells to lose their stem-like properties and die.

"This study brings us back to the fundamental idea that there are many reasons that cancer cells can be aggressive," explains senior author Bradley Bernstein, MD, PhD, of MGH Pathology and the MGH Cancer Center. "Just as normal cells with the same genome differentiate into many different cell types, a single tumor characterized by specific genetic mutations can contain many different types of cells stem-like and more differentiated cells with the difference being rooted in their epigenetic information. Identifying the drivers of these different cellular states in glioblastoma stem cells could offer us the best opportunity for treating what remains an extremely difficult-to -treat tumor."

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Researchers identify transcription factors distinguishing glioblastoma stem cells

Former NIH stem-cell chief joins New York foundation

Nature News Blog

10 Apr 2014 | 22:47 BST | Posted by Sara Reardon | Category: stem cells

Stem-cell biologist Mahendra Rao, who resigned last week as director of the US National Institutes of Healths Center for Regenerative Medicine (CRM), has a new job. On April 9, he was appointed vice-president for regenerative medicine at the New York Stem Cell Foundation (NYSCF), a non-profit organization that funds embryonic stem cell research.

Rao left the National Institutes of Healthabruptly on 28 March, apparently due to disagreements about the number of clinical trials of stem cell therapies that NIHs intramural CRM programme would conduct. CRM was established in 2010 to shepherd therapies using iPS cells adult cells that have been reprogrammed to an embryonic state into clinical translation. One of CRMs potential therapies, which will use iPS cells to treat macular degeneration of the retina, will continue moving toward clinical trials at the NIH, although several others were not funded. NIH officials say that CRM will not continue in its current direction, but the fate of the centers remaining budget and resources is undecided.

Rao says that he wants to move more iPS cell therapies toward trials than NIH had been willing to do. He has already joined the advisory boards of several stem cell therapy companies: Q Therapeutics, a Salt Lake City-based neural stem cell company he co-founded, as well as Cesca Therapeutics formerly known as ThermoGenesis of Rancho Cordova, California, and Stemedica of San Diego, both of which are developing cell-based therapies for cardiac and vascular disorders.

Rao says that his initial focus at NYSCF will be developing iPS cell lines for screening, and formulating a process for making clinical grade cell lines from a patients own cells.

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Former NIH stem-cell chief joins New York foundation