“Latest Stem Cells News”

Abundant precursor cells can become many types of neurons without introducing tumor risk

In a paper published in the April 25 early online edition of the Proceedings of the National Academy of Sciences, researchers at the University of California, San Diego School of Medicine, the Gladstone Institutes in San Francisco and colleagues report a game-changing advance in stem cell science: the creation of long-term, self-renewing, primitive neural precursor cells from human embryonic stem cells (hESCs) that can be directed to become many types of neuron without increased risk of tumor formation.

“It’s a big step forward,” said Kang Zhang, MD, PhD, professor of ophthalmology and human genetics at Shiley Eye Center and director of the Institute for Genomic Medicine, both at UC San Diego. “It means we can generate stable, renewable neural stem cells or downstream products quickly, in great quantities and in a clinical grade – millions in less than a week – that can be used for clinical trials and, eventually, for clinical treatments. Until now, that has not been possible.”

Human embryonic stem cells hold great promise in regenerative medicine due to their ability to become any kind of cell needed to repair and restore damaged tissues. But the potential of hESCs has been constrained by a number of practical problems, not least among them the difficulty of growing sufficient quantities of stable, usable cells and the risk that some of these cells might form tumors.

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An innovative experimental treatment for boosting the effectiveness of blood stem-cell transplants with umbilical cord blood has a favorable safety profile in long-term animal studies, according to Harvard Stem Cell Institute (HSCI) scientists at Dana-Farber Cancer Institute (DFCI), Beth Israel Deaconess Medical Center (BIDMC), and Children’s Hospital Boston (CHB).

Analysis of long-term safety testing in nonhuman primates, published online by the journal Cell Stem Cell in a new section called “Clinical Progress,” revealed that a year following transplant umbilical cord blood units treated with a signaling molecule called 16,16-dimethyl PGE2 reconstituted all the normal types of blood cells, and none of the animals receiving treated cord blood units developed cancer. Wolfram Goessling is the first author of the paper; his HSCI colleague Trista North is the senior author.

The results of long-term safety studies in mice were previously submitted to the Food and Drug Administration to gain permission for a Phase I clinical trial under an investigational new drug (IND) application. Principal investigator Corey Cutler, a Dana-Farber transplant specialist, initiated the trial in 2009 at Dana-Farber and Massachusetts General Hospital. The IND is sponsored by Fate Therapeutics Inc. of San Diego.

Goessling and North were postdoctoral fellows in the laboratory of co-author Leonard Zon, a stem cell researcher at CHB and a scientific founder of Fate Therapeutics, when they hit upon 16,16-dimethyl PGE2 while looking for compounds that could regulate the production of hematopoietic stem cells (blood stem cells). The initial testing made use of zebrafish models.

“This is the first time a compound discovered in zebrafish has received a nod from the FDA for a clinical trial,” said Goessling.

One of the limitations of cord blood as a transplant source is that the cells engraft, or “take,” in the recipient’s bone marrow more slowly than matched donor cells form bone marrow. In addition, there is a higher failure rate for cord blood transplants. Thus there is a need for ways to improve the speed and quality of cord blood transplantation.

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“Generation of a synthetic retina from embryonic stem cells is a landmark discovery that will help enormously our understanding of blinding eye disease” (Professor James Bainbridge of Moorfields Eye Hospital NHS Foundation Trust)

A part of the eye that is essential for vision has been created in the laboratory from animal stem cells, offering hope to the blind and partially sighted.

One day it might be possible to make an eye in a dish, Nature journal reports.

The Japanese team used mouse stem cells – immature cells that have the ability to turn into many types of body tissue (…) A US biotech company has already been granted a license to begin human trials of a stem cell treatment for blindness (…)

Retinitis pigmentosa and age-related macular degeneration (AMD) are the most common causes of blindness in old age, and involve the gradual and normally irreversible destruction of retinal cells.

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CHENNAI – The country’s first public stem cell bank has stopped accepting cord blood donations.

After processing and storing stem cells from cord blood of 569 women since February 2009, Jeevan Stem Cell Bank has put its operations on hold owing to lack of funds. The bank hopes that the situation will soon change, and it can restart operations once more donations come in.

Private banks charge anywhere up to Rs 1.5 lakh for extraction and preservation of these cells, but Jeevan, which started with an initial investment of Rs 3 crore, depends on public goodwill and corporate donations. The stem cells, capable of developing into different kinds of cells and tissues and curing diseases like blood cancer and thalassemia, were planned to be offered for common use.

When the bank began, it aimed at processing and storing at least 30,000 units of stem cells from cord blood by 2014, but for collecting and processing each unit, it cost the bank Rs 30,000. The cost of harvesting cord blood is Rs 8,500 and tissue typing costs Rs 7,000, besides others. “This wasn’t viable without more donations. We have stopped operations,” the stem cell bank’s medical director Saranya Narayan said.

Stem cells have a shelf life of 24 years. “As of now, there is good cure rate from stem cell therapy for some blood-related diseases. The cells may grow damaged tissues or organs. Stem cell therapy has the potential to cure more than 70 medical conditions,” she said.

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Is there a future for stem cell therapies that don’t use embryonic stem cells? An international study involving EPFL has raised doubts, by showing that “reprogramming” adult stem cells leads to genetic aberrations.

It’s a discordant note in the symphony of good news that usually accompanies stem cell research announcements. Stem cells hold enormous promise in regenerative medicine, thanks to their ability to regenerate diseased or damaged tissues. They have made it possible to markedly improve the effectiveness of many medical treatments – muscle regeneration in cases of dystrophy, skin grafts for treating burn victims, and the treatment of leukemia via bone marrow transplants.

The problem is obtaining them. Those that are the true source of life, in the first days of embryonic development, are of course the most highly sought after; still undifferentiated, they are “pluripotent,” meaning they can evolve into liver, muscle, eye – any kind of cell. But the issue of how to obtain them clearly raises insurmountable ethical questions.

“In this regard, the recent discovery of the “reprogramming” phenomenon, by which somatic cells can be induced to convert to a pluripotent state simply by forcing the expression of a few genes, opens a phenomenal number of possibilities in regenerative medicine,” says Didier Trono, Dean of the EPFL School of Life Sciences.

“Imagine, for example, collecting a few cells from the hair follicle of a hemophiliac patient, reprogramming them to the pluripotentiality of their embryonic precursor, correcting the mutation responsible for the coagulation disorder that plagues the patient, and then re-administering them, genetically “cured,” after having orchestrated a differentiation into fully functional progeny.”

Increased risks for cancer?

But a study that has just been published in the journal Cell Death and Differentiation, to be followed by two articles in the journal Nature, is dampening those hopes. Conducted by the Department of Biochemistry at the University of Geneva and the European Institute of Oncology in Milan, with the participation of Trono’s laboratory, it concludes that these reprogrammed cells exhibit a “genomic instability” that appears to be caused by the process used to return the cells to their embryonic state.

Even more serious, the genetic mutations observed resemble mutations that are found in cancer cells. The scientists draw the conclusion that reprogrammed stem cells need to be extensively investigated before they can even be considered for use in regenerative medicine.
The experiments were done using mouse mammary and fibroblast cells. The researchers used three different processes for reprogramming the cells to a “stem,” or embryonic, state. The first method was developed expressly for this study, and the others have already been well documented.

Yet all the processes led to the same, implacable conclusion: the genetic anomalies multiplied, in a manner that seems to indicate that they are inherent to the reprogramming process itself, which typically makes use of oncogenes. “Interestingly, oncogenes have the potential to induce genomic instability,” the authors explain.

These results underline the necessity of conducting further studies. First, to see if the genetic anomalies are serious enough to compromise the function and stability of cells regenerated using the reprogrammed cells; and second, to “refine the methods used for generating induced pluripotent cells, in order to avoid this problem. These results will thus motivate scientists to come up with a solution,” concludes Trono.

from http://goo.gl/elaDN

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Scientists have discovered a new way to generate human motor nerve cells in a development that will help research into motor neurone disease.

A team from the Universities of Edinburgh, Cambridge and Cardiff has created a range of motor neurons – nerves cells that send messages from the brain and spine to other parts of the body – from human embryonic stem cells in the laboratory.

It is the first time that researchers have been able to generate a variety of human motor neurons, which differ in their make-up and display properties depending on where they are located in the spinal cord.

The research, published in the journal Nature Communications, could help scientists better understand motor neurone disease. The process will enable scientists to create different types of motor neurons and study why some are more vulnerable to disease than others.

Motor neurons control muscle activity such as speaking, walking, swallowing and breathing. However, in motor neurone disease – a progressive and ultimately fatal disorder – these cells break down leading to paralysis, difficulty speaking, breathing and swallowing.

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