Disease in a dish approach could aid Huntington's disease discovery

PUBLIC RELEASE DATE:

5-Sep-2014

Contact: Lisa Newbern lisa.newbern@emory.edu 404-727-7709 Emory Health Sciences

Creating induced pluripotent stem cells or iPS cells allows researchers to establish "disease in a dish" models of conditions ranging from Alzheimer's disease to diabetes. Scientists at Yerkes National Primate Research Center have now applied the technology to a model of Huntington's disease (HD) in transgenic nonhuman primates, allowing them to conveniently assess the efficacy of potential therapies on neuronal cells in the laboratory.

The results were published in Stem Cell Reports.

"A highlight of our model is that our progenitor cells and neurons developed cellular features of HD such as intranuclear inclusions of mutant Huntingtin protein, which most of the currently available cell models do not present," says senior author Anthony Chan, PhD, DVM, associate professor of human genetics at Emory University School of Medicine and Yerkes National Primate Research Center. "We could use these features as a readout for therapy using drugs or a genetic manipulation."

Chan and his colleagues were the first in the world to establish a transgenic nonhuman primate model of HD. HD is an inherited neurodegenerative disorder that leads to the appearance of uncontrolled movements and cognitive impairments, usually in adulthood. It is caused by a mutation that introduces an expanded region where one amino acid (glutamine) is repeated dozens of times in the huntingtin protein.

The non-human primate model has extra copies of the huntingtin gene that contains the expanded glutamine repeats. In the non-human primate model, motor and cognitive deficits appear more quickly than in most cases of Huntington's disease in humans, becoming noticeable within the first two years of the monkeys' development.

First author Richard Carter, PhD, a graduate of Emory's Genetics and Molecular Biology doctoral program, and his colleagues created iPS cells from the transgenic monkeys by reprogramming cells derived from the skin or dental pulp. This technique uses retroviruses to introduce reprogramming factors into somatic cells and induces a fraction of them to become pluripotent stem cells. Pluripotent stem cells are able to differentiate into any type of cell in the body, under the right conditions.

Carter and colleagues induced the iPS cells to become neural progenitor cells and then differentiated neurons. The iPS-derived neural cells developed intracellular and intranuclear aggregates of the mutant huntingtin protein, a classic sign of Huntington's pathology, as well as an increased sensitivity to oxidative stress.

Excerpt from:
Disease in a dish approach could aid Huntington's disease discovery

Japan's Riken Reboots After Stem-Cell Scandal

By Dow Jones Business News, August 27, 2014, 12:55:00 AM EDT

TOKYO--A scandal that started with a few suspicious images has led Japan's most prestigious research institute to slash its stem-cell unit by half and acknowledge deeper flaws in its ethics.

The move by the Riken institute came seven months after the publication of papers that it initially hailed as equal in importance to the Copernican revolution in astronomy. Since then, the papers have been retracted, and one of the co- authors committed suicide.

On Wednesday, Riken said it would scale down to half its size the Center for Developmental Biology, rename the center and choose a new director with input from non-Japanese scientists, an indication of how the scandal has damaged the reputation of Japanese science.

"We believe it is important to move forward with the restructuring to improve the quality and promote honest research," said Ryoji Noyori, the Nobel Prize winner who leads Riken.

Riken's overhaul could also sway the field of stem-cell science, which has received billions of dollars in research funds in the hopes of cures for ailments such as diabetes and heart disease.

Some details of the overhaul, including whether anyone beside the director would indeed lose their job, remained murky. Nevertheless, science writer Shinya Midori said, "This could trigger scaling down in the field of regenerative medicine."

The scandal at Riken has deeply shaken the country's science establishment and the wider stem-cell world and sparked a debate about research ethics in Japan amid "results-first" pressure.

The drama has focused on the institute's 14-year-old developmental-biology center and erupted after one of its scientists, Haruko Obokata, was found guilty of manipulating data in a pair of papers published in the journal Nature. The studies, which claimed to show a groundbreaking method of making stem cells by dipping cells in a mild acid solution, were quickly challenged and Nature retracted the papers in July, saying they contained inaccurate data.

Riken initially stood by the 31-year-old Dr. Obokata, who had been hailed as a national hero after her research was first published, but later distanced itself from what it called her "sloppy data management" and poor research ethics.

Go here to read the rest:
Japan's Riken Reboots After Stem-Cell Scandal

Pfizer buys into Cambridge life science innovation

Stem cell technology pioneer,DefiniGEN Ltdhas joined the Pfizer-inspired European Bank for induced pluripotent stem cells (EBiSC) consortium.

The consortium comprises 26 partners, and has been newly-formed with support from the Innovative Medicines Initiative (IMI) and the European Federation of Pharmaceutical Industries and Associations (EFPIA).

DefiniGen, a Cambridge University spin-out that has raised millions, represents one of the first commercial opportunities to arise from the universitys expertise in stem cells and is based on the research of Dr Ludovic Vallier, Dr Tamir Rashid and Professor Roger Pedersen of the universitys Anne McLaren Laboratory of Regenerative Medicine.

The EBiSC iPS cell bank will act as a central storage and distribution facility for human iPS cells, to be used by researchers across academia and industry in the study of disease and the development of new therapeutics. DefiniGENs role will be to validate EBiSC iPS cell lines by generating liver hepatocyte cells for toxicology, disease modelling, and regenerative medicine applications.

Dr Marcus Yeo, CEO of DefiniGEN, said: We are delighted to be a part of this ground-breaking consortium which will provide a crucial platform resource to enable the realisation of the full potential of iPS technology.

Conceptualised and coordinated by Pfizer Ltd in Cambridge, UK and managed by Roslin Cells Ltd in Edinburgh, the EBiSC bank aims to become the European go to resource for high quality research grade human iPS cells.

Today, iPS cells are being created in an increasing number of research programmes underway in Europe, but are not being systematically catalogued and distributed at the necessary scale to keep pace with their generation, nor to meet future demand.

The 35 million project will support the initial build of a robust, reliable supply chain from the generation of customised cell lines, the specification to internationally accepted quality criteria and their distribution to any global qualified user, ensuring accessibility to consistent, high quality tools for new medicines development.

Ruth McKernan, CSO of Pfizers Neusentis research unit in Cambridge, said: We are excited to be a part of this precompetitive collaboration to build a sustainable repository of high quality human iPS cell lines.

For many areas of research in academia and in industry, understanding the biological basis of disease heterogeneity is the next horizon. A bank of well-characterised iPS lines with strong relevance to the entire research community will help us all in our mission to bring therapies to patients.

View post:
Pfizer buys into Cambridge life science innovation

Can stem cells help mobility after stroke?

MIAMI - When Bruce Daily woke up after having lumbar surgery a year ago, he realized he couldn't move the right side of his body.

"It took me a long while to figure out I wasn't gonna walk again," he said. "I knew I was down."

Daily, 69, had gone in for lumbar surgery at the University of Miami hospital and had an ischemic stroke while under anesthesia. An ischemic stroke results from an obstruction in a blood vessel that blocks the blood from getting to the brain.

Because he was unconscious, he missed the four-to-five hour-window to apply the tissue plasminogen activator, or tPA, the only medication available to treat ischemic strokes. The medication dissolves the clot, restoring blood flow to the brain.

But while he missed that chance, he was right on time to meet Dr. Dileep Yavagal, a neurosurgeon who practices at the University of Miami and Jackson Memorial hospitals. Yavagal was enrolling patients in RECOVER-stroke, a clinical trial treating recent stroke patients with stem cells from their bone marrow and applying them directly into the carotid artery, one of two arteries that supply the neck and head with blood. Daily was one of 47 patients nationwide who qualified for the study.

The study is funded by Cytomedix, the company that developed the technology to extract stem cells from bone marrow. The firm chose Yavagal to lead a national blind study at the end of 2012.

Yavagal enrolled 13 patients at the University of Miami/Jackson Memorial Hospital, between the end of 2012 and January of 2014. So far, the initial three-month results have revealed that the marrow cells are not doing any damage, and there was no clear difference between those who received the cells and those who didn't. The study's one-year final results will be revealed in January.

"There is severe need for developing treatment for ischemic stroke, and stem cells are the most promising," said Yavagal, whose own research is still in its initial phase, focusing on using a healthy donor's bone marrow stem cells versus the patient's own marrow.

Stroke, the leading cause of adult disability in the United States, and the No. 4 cause of death in the country, causes 130,000 deaths a year in the U.S., according to the Centers for Disease Control and Prevention.

Yavagal, associate professor of clinical neurology and neurosurgery and the director of interventional neurology at the University of Miami's Miller School of Medicine, said that restricted mobility or loss of speech resulting from a moderate to severe stroke can be devastating because patients often become dependent on someone else for daily activities.

View post:
Can stem cells help mobility after stroke?

Method developed to print replacement tissues using stem cells

Prof Frank Barry, scientific director of the Regenerative Medicine Institute at NUI Galway, with PhD student Babu Rajendra Prasad. Photograph: Joe OShaughnessy

By using tiny cartridges dispensing one stem cell at a time, Galway-based researchers may soon be able to literally print the scaffold of a healthy human tissue, and let it grow to become a therapeutic transplant.

When the Regenerative Medicine Institute at NUI Galway and Irish start-up company Poly-Pico Ltd recently joined forces for a trial proof-of-concept experiment, the results were spectacular.

They were able to dispense tiny drops from a cartridge filled with a stem cell mixture, each drop containing no more than a single stem cell.

Now imagine that we have five dispensing cartridges, each containing a different type of programmed stem cell, said Frank Barry, professor of cellular therapy and scientific director of the institute.

In principle we could essentially print them on to a surface and, by repeating the process a few thousands of times, obtain a mixture of growing cells and eventually a healthy pancreatic islet.

The islets produced by the printing process would then be transplanted into the pancreas of a Type 1 diabetic patient. The hope is that they will develop there and eventually help with the regulation of blood sugar levels.

It is a futuristic prospect, but it is not science fiction, Prof Barry said.

We are talking five years down the line for potential clinical trials.

In the experiment, the drops containing a single stem cell were easily identified and isolated. The cells were then allowed to replicate themselves into exact copies. Finally the researchers checked that they had remained viable and unaffected by the process.

More here:
Method developed to print replacement tissues using stem cells

DO STEM CELL TREATMENTS WORK? | The Stem Cell Blog

ADULT, amputat, clinical trial, CURE, DIABETES, fda, heal, heart, MS, multiple sclerosis, PALSY, RESEARCH, stem cell, stroke, therapy, TREATMENT

DO STEM CELL TREATMENTS WORK?

Do not take one step further in your plans for treatment or read one more word about stem cells anywhere else until you believe that we have answered this question, unequivocally and without a shadow of a doubt:

Ask most US doctors if repair stem cell treatments work and they will tell you NO! You may also get condescending retorts, misinformation and derisive abuse. But if you press them on the question, eventually they will give you the reason why they believe repair stem cells dont work. The top answer WHY STEM CELLS DONT WORK is (Survey Says!):

There have been no clinical trials to date that prove they do work.

When all is said and done, in the end, there is nothing that will convince a western doctor of the effectiveness of stem cell treatments besides clinical trials. So have there been any stem cell clinical trials? Is all of the evidence supporting the benefits of stem cell treatments anecdotal as virtually every western doctor says? NOT ON YOUR LIFE! Have there been clinical trials? The answer is a resounding YES!

According to the National Institutes of Health, there were and are ~2600 stem cell clinical trials around the world http://www.clinicaltrials.gov/

Lets look at (only) a few of those ~1300 clinical trials:

Other stroke articles:

Read the original here:
DO STEM CELL TREATMENTS WORK? | The Stem Cell Blog

ViaCyte gets $20M for diabetes therapy trials

Human embryonic stem cells were differentiated into cells of the pancreas (blue). These cells give rise to insulin-producing cells (red). When implanted into mice, the stem cell-derived pancreatic cells effectively replace the insulin lost in type 1 diabetes. San Diego-based ViaCyte is developing an implantable artificial pancreas derived from human embryonic stem cells. Its work is funded in part by grants from the California Institute for Regenerative Medicine.

San Diego's ViaCyte has received $20 million from a drug company to advance its stem cell-based therapy for type 1 diabetes into clinical trials.

ViaCyte's agreement with Janssen Pharmaceuticals, a Johnson & Johnson company, comes days after the company announced receiving the go-ahead from the U.S. Food and Drug Administration to begin clinical trials. The agreement also includes the company's investment fund, Johnson & Johnson Development Corporation.

ViaCyte's experimental product, VC-01, is derived from human embryonic stem cells. These cells are matured into cells that regulate blood sugar levels. These includes cells that make insulin, which lowers blood sugar, in addition to cells that make glucagon, which raises blood sugar levels. It's believed that recreating this natural complement of hormones will be more effective than administering insulin alone.

The cells are encapsulated into a semi-permeable pouch that allows the hormones to enter the bloodstream, and nutrients from the bloodstream to enter cells, but keeps out the immune system, which would otherwise attack the cells.

The California Institute for Regenerative Medicine (CIRM), the states stem cell agency, has awarded ViaCyte more than $38 million to help develop the treatment over the past six years.

The money will mostly be used to advance clinical development of the product, ViaCyte said. The agreement also gives Janssen the right to "consider a longer-term transaction" related to the product.

This is excellent news as it demonstrates that pharmaceutical companies are recognizing stem cell therapies hold tremendous promise and need to be part of their development portfolio, CIRM president and CEO C. Randal Mills said in a statement. This kind of serious financial commitment from industry is vital in helping get promising therapies like this through all the phases of clinical trials and, most importantly, to the patients in need.

ViaCyte had also recently received $5.4 million in private equity financing.

These important transactions provide us with the additional resources we need to pursue the further development of the VC-01 product candidate as a potential new treatment option for patients with type 1 diabetes, said Paul Laikind, Ph.D., ViaCyte's president and CEO, in the statement. We are pleased to be extending our relationship with Janssen and JJDC is this area of mutual interest.

Go here to read the rest:
ViaCyte gets $20M for diabetes therapy trials

VIACYTE CLINICAL TRIAL OKD

By Bradley J. Fikes U-T5:06 a.m.Aug. 20, 2014

ViaCyte of San Diego has received permission from the Food and Drug Administration to try its stem cell-based diabetes therapy.

The combination clinical trial phases 1 and 2 will aim to determine the safety level of the therapy and look for early signs of efficacy.

ViaCyte grows replacement insulin-producing cells from human embryonic stem cells, which are placed in a semipermeable pouch. The pouch will be implanted into patients, allowing insulin and other hormones to enter their bloodstream. The pouch and cells are together called VC-01.

The product has the potential to provide a virtual cure for Type 1 diabetes, ViaCyte officials said.

Clinical testing in animals has shown that the replacement cells successfully duplicate the function of insulin-producing beta cells. They secrete not only insulin, which lowers blood sugar, but hormones such as glucagon, which raises it. Providing a range of hormones as in the natural pancreas is expected to provide better control of blood sugar than with insulin alone.

The FDA green light is not only good news for privately held ViaCyte, but also for the states stem cell agency, the California Institute for Regenerative Medicine. The agency, which has granted ViaCyte more than $38 million to research and develop the treatment, has been under pressure in recent years to show that its $3 billion in bond funding is leading to therapies.

(The institute) was created to help develop stem cell treatments for diseases that are currently incurable with traditional approaches, C. Randal Mills, president and CEO of the agency, said in a statement. Anytime a product, particularly one as innovative as this one, progresses from the lab and into clinical trials, its very encouraging news.

Inadequate control of blood sugar increases the risk of heart disease, stroke, kidney failure and other complications from diabetes.

The ViaCyte product contains immature beta cells grown from embryonic stem cells. After implantation, the cells mature and begin to release the appropriate hormones in response to blood sugar levels.

More:
VIACYTE CLINICAL TRIAL OKD

Stem cell study reveals how genetic variations linked to mental illness affects neuron

A new study of stem cells has revealed how a genetic variation linked to schizophrenia, bipolar disorder and severe depression affects connections among neurons in the developing brain.

According to the study led by Guo-li Ming and Hongjun Song of the Johns Hopkins University School of Medicine, using stem cells generated from people with and without mental illness to observe the effects of a rare and pernicious genetic variation on young brain cells found that several major mental illnesses have common roots in faulty "wiring" during early brain development.

Ming said that this was the next best thing to going back in time to see what happened while a person was in the womb to later cause mental illness and they found the most convincing evidence yet that the answer lies in the synapses that connect brain cells to one another.

One difficulty in studying the genetics of common mental illnesses is that they are generally caused by environmental factors in combination with multiple gene variants, any one of which usually could not by itself cause disease. A rare exception is the gene known as disrupted in schizophrenia 1 (DISC1), in which some mutations have a strong effect. Two families have been found in which many members with the DISC1 mutations have mental illness.

To find out how a DISC1 variation with a few deleted DNA "letters" affects the developing brain, the research team collected skin cells from a mother and daughter in one of these families who have neither the variation nor mental illness, as well as the father, who has the variation and severe depression, and another daughter, who carries the variation and has schizophrenia. For comparison, they also collected samples from an unrelated healthy person. Postdoctoral fellow Zhexing Wen, Ph.D., coaxed the skin cells to form five lines of stem cells and to mature into very pure populations of synapse-forming neurons.

After growing the neurons in a dish for six weeks, collaborators at Pennsylvania State University measured their electrical activity and found that neurons with the DISC1 variation had about half the number of synapses as those without the variation.

To find out how DISC1 acts on synapses, the researchers also compared the activity levels of genes in the healthy neurons to those with the variation and found that the activities of more than 100 genes were different and the researchers added that this is the first indication that DISC1 regulates the activity of a large number of genes, many of which are related to synapses.

The study was published online in the journal Nature.

(Posted on 18-08-2014)

Read the original here:
Stem cell study reveals how genetic variations linked to mental illness affects neuron

Stem cells reveal how illness-linked genetic variation affects neurons

A genetic variation linked to schizophrenia, bipolar disorder and severe depression wreaks havoc on connections among neurons in the developing brain, a team of researchers reports. The study, led by Guo-li Ming, M.D., Ph.D., and Hongjun Song, Ph.D., of the Johns Hopkins University School of Medicine and described online Aug. 17 in the journal Nature, used stem cells generated from people with and without mental illness to observe the effects of a rare and pernicious genetic variation on young brain cells. The results add to evidence that several major mental illnesses have common roots in faulty "wiring" during early brain development.

"This was the next best thing to going back in time to see what happened while a person was in the womb to later cause mental illness," says Ming. "We found the most convincing evidence yet that the answer lies in the synapses that connect brain cells to one another."

Previous evidence for the relationship came from autopsies and from studies suggesting that some genetic variants that affect synapses also increase the chance of mental illness. But those studies could not show a direct cause-and-effect relationship, Ming says.

One difficulty in studying the genetics of common mental illnesses is that they are generally caused by environmental factors in combination with multiple gene variants, any one of which usually could not by itself cause disease. A rare exception is the gene known as disrupted in schizophrenia 1 (DISC1), in which some mutations have a strong effect. Two families have been found in which many members with the DISC1 mutations have mental illness.

To find out how a DISC1 variation with a few deleted DNA "letters" affects the developing brain, the research team collected skin cells from a mother and daughter in one of these families who have neither the variation nor mental illness, as well as the father, who has the variation and severe depression, and another daughter, who carries the variation and has schizophrenia. For comparison, they also collected samples from an unrelated healthy person. Postdoctoral fellow Zhexing Wen, Ph.D., coaxed the skin cells to form five lines of stem cells and to mature into very pure populations of synapse-forming neurons.

After growing the neurons in a dish for six weeks, collaborators at Pennsylvania State University measured their electrical activity and found that neurons with the DISC1 variation had about half the number of synapses as those without the variation. To make sure that the differences were really due to the DISC1 variation and not to other genetic differences, graduate student Ha Nam Nguyen spent two years making targeted genetic changes to three of the stem cell lines.

In one of the cell lines with the variation, he swapped out the DISC1 gene for a healthy version. He also inserted the disease-causing variation into one healthy cell line from a family member, as well as the cell line from the unrelated control. Sure enough, the researchers report, the cells without the variation now grew the normal amount of synapses, while those with the inserted mutation had half as many.

"We had our definitive answer to whether this DISC1 variation is responsible for the reduced synapse growth," Ming says.

To find out how DISC1 acts on synapses, the researchers also compared the activity levels of genes in the healthy neurons to those with the variation. To their surprise, the activities of more than 100 genes were different. "This is the first indication that DISC1 regulates the activity of a large number of genes, many of which are related to synapses," Ming says.

The research team is now looking more closely at other genes that are linked to mental disorders. By better understanding the roots of mental illness, they hope to eventually develop better treatments for it, Ming says.

More here:
Stem cells reveal how illness-linked genetic variation affects neurons