Monthly Archives: October 2011

Are we finally able to repair our own organs?

 The dream of regenerating human organs is as old as Prometheus. Chained to his rock, the Titan survived attacks by an eagle that feasted on his liver by growing it anew under cover of darkness. When Mary Shelley wrote Frankenstein, her shocker on the creation of life, she gave it the alternative title The Modern Prometheus.

But myths have a habit of becoming reality, and life of imitating art. For more than a decade we have been seduced by the idea that it may truly be possible to recreate organs. Our response to this possibility incorporates both the Promethean dream and the Frankenstein nightmare, inspiring hope and fear in almost equal measure.

But although talk has been plentiful, progress appears slow. For every advance in the science of stem cells, there has been a retreat. It is plain that unlike, say, the invention of vaccination, this is not going to be a “quick and dirty” victory achieved without a deep scientific understanding. Vaccination worked long before there was any real knowledge of the immune system that made it work. But it does not seem that the stem cell scientists will be so lucky.

Stem cells are the wellsprings of life. Unlike the specialised cells of the skin, the muscle, or the brain, which have narrowly defined functions, stem cells are full of infinite possibilities. They can develop, given the right setting, into any of those specialized cells. In theory, they could replace those lost by age or illness just as Prometheus regenerated his liver. They are “pluripotent”, in the jargon.

The obvious place to find them is in the embryo, the small bundle of cells produced by the fertilisation of egg by sperm that will develop into a human being. In 1981, two teams independently isolated embryonic stem cells from mice and, in 1998, a technique was developed to isolate and grow human stem cells in tissue culture, which were able to create the huge number of cells needed for clinical interventions. The stage appeared set for stem cell treatments to transform medicine.

More than a decade later, a more sober mood prevails. Embryonic stem cells are finally in clinical trials but it has been a long road, both scientifically and politically. Ethical question marks over the morality of using human embryos halted public backing for the research for many years in the US, science’s greatest powerhouse, and diverted attention instead to the idea of transforming adult cells back into a class of cells called induced pluripotent stem cells (iPS cells). By winding the clock back, it is possible for iPS cells to regain the qualities of those present at the beginning of life, and bypass the moral dilemmas.

Cells of this sort were the first to achieve some success. In 2007, mice with sickle cell anaemia were cured by infusing them with iPS cells created from their own skin and modified by gene-splicing techniques so that they no longer contained the sickle-cell gene. It was a brilliant proof of principle, but mice are not men. The technique cannot be used in humans because the genetically-modified viruses used to create the iPS cells could trigger cancer.

Several routes to iPS cells have been tried to get round these difficulties. At first, it seemed that embryonic stem cells could be made by implanting the nucleus of a patient’s adult cell into an unfertilized human egg whose nucleus had been removed – the same technique as cloning. But the method would require hundreds of eggs for each patient. In 2007, Shinya Yamanaka of Kyoto University found that by injecting four protein factors into the adult cell he made it revert to the embryonic state. But these cells appear to retain a memory of their previous identity that denies them pluripotency.

The latest twist came earlier this month when a team from New York Stem Cell Foundation Laboratory led by Dr Dieter Egli announced a new way of making iPS cells using human eggs. Their technique differed because they did not first remove the nucleus of the egg before inserting the adult cell. To their surprise, it worked: an embryo developed to the blastocyst stage, which enabled stem cells to be harvested. But the resultant cells are useless for therapy, because they still contain the extra set of chromosomes from the original egg nucleus. This was, said Robin Lovell-Badge of the National Institute for Medical Research: “An ending that still falls short of the original aim – they did not obtain useful cell lines. However, the work may reveal a way to overcome some problems.”

While iPS therapy has been stalled, more direct approaches to rebuilding the body have achieved some success. In July this year, a man was given the world’s first synthetic windpipe in an operation at the Karolinska University Hospital in Stockholm. Made from a special polymer developed at University College London, it was coated with cells taken from the patient’s bone marrow, which were persuaded to transform themselves into tracheal lining cells. Similar techniques have been used to create artificial urethras and larynxes.

These are not pluripotent stem cells, but clearly possess some ability to adapt to their circumstances. The same is true of the cells taken from fat and bone marrow, which were used recently to treat the injured elbow of baseball player Bartolo Colon, or those used for the hearts of patients who have suffered heart attacks (see box). But what of true embryonic stem cells? The embargo on publicly funded research during the Bush years prevented much progress, but the first clinical trials have finally been launched in the US and Europe.

In September, the UK approved a clinical trial of embryonic stem cells at London’s Moorfields Eye Hospital, using a cell line developed by the US company Advanced Cell Technology. They will be injected into the eyes of a dozen patients with Starguard’s macular dystrophy, a disease that strikes between the age of 10 and 20 and causes progressive vision loss. A similar trial was approved in the US last year, and the first patients were treated in July. Robert Lanza, the company’s chief scientific officer, said: “We’re hoping to prevent the onset of blindness altogether in those patients.” He hopes to launch a second UK trial soon for age-related macular degeneration, a much more common condition.

In the US, another private company, Geron, last year launched a trial of a new cell therapy designed to repair spinal injuries. It uses oligodendrocyte progenitor cells – precursors of nerve cells – that are made from embryonic stem cells. So far, four patients have been treated.

And in Glasgow, a trial of cells to treat stroke was also launched last year, using nerve cells produced by the company ReNeuron. It aims to evaluate the safety of the treatment, and several patients have so far been given low doses.

These are all early-stage trials, designed in the first place to test safety, though hoping also to show some benefits. None has yet to report any results, but at last stem cells have reached the clinic. In the next few years many more trials will be started and we will learn whether the high hopes of stem cell therapy have been realised or whether – like gene therapy, its equally hyped predecessor – it will prove a disappointment.

Fat that heals hearts

Cells extracted from the fat of heart attack patients and injected into the damaged parts of their hearts have shown small but sustained benefits. A trial of 14 patients reported in June that the areas of heart damage were 11% smaller, and the heart’s pumping efficiency 6% greater, in those treated with the cells than those treated with placebo. The improvements had been sustained after the injections ceased, said Dr Henricus Duckers of the Erasmus Medical Centre in Rotterdam.

“This is quite important, because the big thing about cell therapy trials is whether the effect is transient or will be seen on long-term follow-up. We show that if you protect the muscle in the acute phase of a heart attack, you will indeed have sustained improvement.”

The trial used cells called adipose-derived regenerative cells (ADRCs) obtained by liposuction from the patients’ own fat in a process taking about 30 minutes. It takes an hour to separate the AERCs from the fat, using a process developed by Cytori Therapeutics, before they are administered through a fine catheter to the area of damage. The trial continues.Cells extracted from the fat of heart attack patients and injected into the damaged parts of their hearts have shown small but sustained benefits. A trial of 14 patients reported in June that the areas of heart damage were 11% smaller, and the heart’s pumping efficiency 6% greater, in those treated with the cells than those treated with placebo. The improvements had been sustained after the injections ceased, said Dr Henricus Duckers of the Erasmus Medical Centre in Rotterdam.

“This is quite important, because the big thing about cell therapy trials is whether the effect is transient or will be seen on long-term follow-up. We show that if you protect the muscle in the acute phase of a heart attack, you will indeed have sustained improvement.”

 

Source:

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Scientists Identify Stem Cell Key to Lung Regeneration

Scientists at A*STAR’S Genome Institute of Singapore (GIS) and Institute of Molecular Biology (IMB), have made a breakthrough discovery in the understanding of lung regeneration. Their research showed for the first time that distal airway stem cells (DASCs), a specific type of stem cells in the lungs, are involved in forming new alveoli to replace and repair damaged lung tissue, providing a firm foundation for understanding lung regeneration.

Lung damage is caused by a wide range of lung diseases including influenza infections and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). Influenza infection induces acute respiratory distress syndrome (ARDS) which affects more than 150,000 patients a year in the US, with a death rate of up to 50 percent. COPD is the fifth biggest killer worldwide.

The team took a novel approach in tackling the question of lung regeneration. They cloned adult stem cells taken from three different parts of the lungs – nasal epithelial stem cells (NESCs), tracheal airway stem cells (TASCs) and distal airway stem cells (DASCs). Despite the three types of cells being nearly 99 percent genetically identical, the team made the surprising observation that only DASCs formed alveoli when cloned in vitro.

“We are the first researchers to demonstrate that adult stem cells are intrinsically committed and will only differentiate into the specific cell type they originated from. In this case, only DASCs formed alveoli because alveolar cells are found in the distal airways, not in the nasal epithelial or tracheal airway”, said Dr Wa Xian, Principal Investigator at IMB. “This is a big advancement in the understanding of adult stem cells that will encourage further research into their potential for regenerative medicine.”

Using a mouse model of influenza, the team showed that after infection, DASCs rapidly grow and migrate to influenza-damaged lung areas where they form “pods”. These “pods” mature to new alveoli which replace the alveoli that were destroyed by the infection, leading to lung regeneration.

“We have harvested these “pods” to provide insight into genes and secreted factors that likely represent key components in tissue regeneration. These secreted factors might be used as biological drugs (biologics) to enhance regeneration of the lung and airways,” said Dr Frank McKeon, Senior Group Leader of the Stem Cell and Developmental Biology at GIS.

The research was jointly led by Dr Frank McKeon from GIS and Dr Wa Xian from IMB in collaboration with scientists at the National University of Singapore (NUS), and clinicians at the Harvard Medical School and the Brigham and Women’s Hospital in Boston.

Prof Birgitte Lane, Executive Director of IMB, said, “This groundbreaking work is a fine example of collaborative research, which has brought us new insight into lung epithelial stem cells. This will have breakthrough consequences in many areas.” Dr Edison Liu, Executive Director of GIS, added, “We will continue to seek impactful collaborations and build upon this research area where there is a need for novel therapies, which will offer hope for patients suffering from respiratory diseases.”

via http://biosciencetechnology.com


Breastmilk, A Natural Stem Cell Therapy

 Human breastmilk has the potential to help people suffering from diseases including Parkinson’s disease and diabetes, according to a researcher at The University of Western Australia.

Dr Foteini Hassiotou presented her findings at the National finals at the 2011 AusBiotech Conference in Adelaide this weekend and was last night judged the national winner of the AusBiotech-GSK Student Excellence Awards.

Dr Hassiotou, a member of the UWA Hartmann Human Lactation Research Group, has discovered that human breastmilk contains stem cells which are able to turn into not only breast cells, but also cells of the bone, cartilage, fat, brain, liver and pancreas, depending on the medium in which they are grown.

“The benefit of obtaining stem cells from breastmilk is that they can be accessed non-invasively, unlike getting them from the bone marrow, umbilical cord blood or peripheral blood,” she said.

“If we can understand the properties of these cells and their role in the breast and in the breast-fed baby, we can use them as models for breast cancer research and in innovative stem cell therapies.

Stem cell therapy is a very promising technology.  Every year there are more than 1,000 stem cell transplants in Australia and over 60,000 around the world.  The limitations of the current therapies are that the transplanted stem cells are accessed using invasive methods and have limited differentiation potential.  Breastmilk offers a new exciting opportunity for stem cell therapies, with the potential to benefit not only the mother and child, but also other people.”

Dr Hassiotou said that she is currently examining the in vivo transplantation potential of milk stem cells into animals.

Her supervisors are Winthrop Professor Peter Hartmann, head of the 30-year old Human Lactation Research Group of UWA, and Professor Luis Filgueira, an expert in cell development and function.

Source: The University of Western Australia http://bit.ly/q8Qr6a


Stem Cell Therapy Helps Pets in Pain

The healing power of stem cells is now helping dogs in pain. Vets are excited about this new therapy that’s making a big difference for South Texans’ beloved pets.

Oscar is an 11-year-old Australian Terrier, an agility competitor that suffered from osteoarthritis, impacting his usual exuberant nature.
“He was starting to really slow down and he was starting to suffer,” said Oscar’s owner, Judy Larson of San Antonio.
Instead of medications that provide only marginal relief and create side effects, Larson turned to the Perrin/410 Animal Hospital for help. Doctors performed a new procedure called Adipose Stem Cell Therapy.
“We treat the fat, process it, activate it, and then inject it back into the animal the same day,” explained veterinarian Dr. Bryan Stuckey.
The procedure takes about four hours. Doctors first harvest fat tissue from the abdomen. Then, they process it and activate the stem cells. Injections back into the joint promote regeneration of the damaged areas in the bone, cartilage, ligaments and tendons.
“And with this, there is no side effect,” Stuckey said. “There’s no harmful side effect. It’s from the animal itself. It’s injected back in so there is no donor involved.”
Pets start to show improvement in two weeks, and continue to get better over the next two to three months.
“It was time going backwards,” Larson stated. “You know, his eyes cleared up. He started to grow hair again. His energy level went back up. His appetite. It was like getting my dog back.”
The cost is about $2,000. Vets say the procedure pays for itself in about two years, since dogs no longer need expensive medications and tests.
Stuckey has treated 16 dogs this way so far. He calls it a huge advancement in pain management.
“We can’t cure a bad joint, but we can fix it so it does not hurt as much,” he commented.
Stem cell therapy won’t necessarily extend a dog’s life. But vets say their quality of life will improve. And that can make all the difference for an animal in pain.

by Wendy Rigby / KENS 5

khou.com


Stem Cell Therapy Helps Pets in Pain

 The healing power of stem cells is now helping dogs in pain. Vets are excited about this new therapy that’s making a big difference for South Texans’ beloved pets.

Oscar is an 11-year-old Australian Terrier, an agility competitor that suffered from osteoarthritis, impacting his usual exuberant nature.
“He was starting to really slow down and he was starting to suffer,” said Oscar’s owner, Judy Larson of San Antonio.
Instead of medications that provide only marginal relief and create side effects, Larson turned to the Perrin/410 Animal Hospital for help. Doctors performed a new procedure called Adipose Stem Cell Therapy.
“We treat the fat, process it, activate it, and then inject it back into the animal the same day,” explained veterinarian Dr. Bryan Stuckey.
The procedure takes about four hours. Doctors first harvest fat tissue from the abdomen. Then, they process it and activate the stem cells. Injections back into the joint promote regeneration of the damaged areas in the bone, cartilage, ligaments and tendons.
“And with this, there is no side effect,” Stuckey said. “There’s no harmful side effect. It’s from the animal itself. It’s injected back in so there is no donor involved.”
Pets start to show improvement in two weeks, and continue to get better over the next two to three months.
“It was time going backwards,” Larson stated. “You know, his eyes cleared up. He started to grow hair again. His energy level went back up. His appetite. It was like getting my dog back.”
The cost is about $2,000. Vets say the procedure pays for itself in about two years, since dogs no longer need expensive medications and tests.
Stuckey has treated 16 dogs this way so far. He calls it a huge advancement in pain management.
“We can’t cure a bad joint, but we can fix it so it does not hurt as much,” he commented.
Stem cell therapy won’t necessarily extend a dog’s life. But vets say their quality of life will improve. And that can make all the difference for an animal in pain.

by Wendy Rigby / KENS 5

khou.com

Posted on October 5, 2011 at 3:09 PM


Adult Stem Cells from Cord Blood Could Help Repair Damaged Heart Muscle

At least 20 million people survive heart attacks and strokes every year, according to World Health Organization estimates, but many have poor life expectancy and require continual costly clinical care. 

The use of a patient’s own stem cells may repair heart attacks, although their benefit may be limited due to scarce availability and ageing. The researchers have found heart muscle-like cells grown using stem cells from human umbilical cord blood could help repair heart muscle cells damaged by a heart attack.

The study, led by Professor Raimondo Ascione, Chair of Cardiac Surgery & Translational Research in the School of Clinical Sciences at the University of Bristol, is published online in Stem Cell Reviews & Reports.

The study, funded by the British Heart Foundation (BHF) and the National Institute for Health Research (NIHR), found that it is possible to expand up to seven-fold, in vitro, rare stem cells (called CD133+) from human cord blood and then grow them into cardiac muscle cells.

The findings could have major implications on future treatment following a heart attack given that cells obtained from adults following a heart attack may be less functional due to ageing and risk factors.

Professor Ascione said: “We believe our study represents a significant advancement and overcomes the technical hurdle of deriving cardiac muscle-type cells from human cord blood. The method we have found has the attributes of simplicity and consistency. This will permit more robust manipulation of these cells towards better cell homing and cardiac repair in patients with myocardial infarction.

“Our research suggests that in the future stem cells derived from cord blood bank facilities might be used for repair after a heart attack.”

The study focused on a rare type of stem cells, called CD133+, which is also present in adult bone marrow. There is also strong experimental evidence these cells derived from bone marrow may help with the regeneration of damaged heart muscle.

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said: “Regenerative medicine research in the lab, alongside studies of patients, is absolutely crucial. Right now, the damage to the heart caused by heart attack cannot be reversed. Through research like this across the UK, we hope to bring our vision of mending broken hearts to reality.

“There has been interest for some time in the potential use of blood from the umbilical cord as a source of stem cells for therapy in a variety of diseases. This study has shown for the first time that it’s possible to turn cord blood stem cells into cells that look like heart muscle, in the lab. The results are encouraging, but there are still lots of questions to answer before we’ll know whether these cells can be used successfully for heart repair in patients.”

In 2007, the British Heart Foundation (BHF) awarded Professor Ascione, over £200,000 for the world’s first clinical trial, TransACT, to test whether bone marrow derived CD133+ stem cells can repair heart muscle cells damaged by a heart attack. Recently, funding for the trial has been extended to 2013.

The double blind placebo-controlled trial has successfully recruited 50 per cent of its patients with no safety concerns. Under Professor Ascione’s leadership, 31 out of 60 patients, who have suffered a major heart attack, have been injected to date at the Bristol Heart Institute with stem cells from their own bone marrow or a placebo into their damaged hearts during routine coronary bypass surgery.


Gene Therapy and Stem Cells Unite

Two of the holy grails of medicine – stem cell technology and precision gene therapy – have been united for the first time in humans, say scientists.

It means patients with a genetic disease could, one day, be treated with their own cells. 

A study in Nature corrected a mutation in stem cells made from a patient with a liver disease.

Researchers said this was a “critical step” towards devising treatments, but safety tests were still needed.

At the moment, stem cells created from a patient with a genetic illness cannot be used to cure the disease as those cells would also contain the corrupted genetic code.

Scientists, at the Wellcome Trust Sanger Institute and the University of Cambridge, were working on cirrhotic liver disease.

It is caused by a change to a single pair of letters, out of the six billion which make up the genetic code.

As a result, a protein which protects the body from damage, antitrypsin, cannot escape from the liver where it is made.

The illness is one of the most common genetic diseases, affecting one in 2,000 people in Europe.

The only solution is a liver transplant, but this requires a lifetime of drugs to prevent organ rejection.

The research group took a skin cell from a patient and converted it to a stem cell.

A molecular scalpel was used to cut out the single mutation and insert the right letter – correcting the genetic fault.

The stem cells were then turned into liver cells. One of the lead researchers, Prof David Lomas, said: “They functioned beautifully with normal secretion and function”.

When the cells were placed into mice, they were still working correctly six weeks later.

‘Enormous potential’

Prof Lomas said if this could be developed into a therapy it would be preferable to liver transplant as the patient would not need to take immunosuppressant drugs.

He told the BBC that the technique was “ridiculously hard,” yet “the potential is enormous, but only time will tell”.

Further animal studies and human clinical trials would be needed before any treatment as “the key thing is safety”.

For example, concerns have been raised about “induced” stem cells being prone to expressing cancer causing genes.

Prof Robin Ali, from University College London and the Medical Research Council’s stem cell translational research committee, said: “It’s very interesting.

“Most gene therapy is not correcting the gene, it’s introducing a new copy of the gene, what’s exciting is that this corrects.

“The big problem with individualised medicine is the cost – that is one of the major barriers.”

 

by James Gallagher

Health Reporter, BBC News