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Are you or a loved one interested in receiving stem cell treatment? For free information, please fill out our treatment form or email me don@repairstemcells.org and just put TREATMENT in the subject box and the MEDICAL CONDITION in the message.
NIH scientists find that restocking new cells in the brain’s center for smell maintains crucial circuitry.

For decades, scientists thought that neurons in the brain were born only during the early development period and could not be replenished.  More recently, however, they discovered cells with the ability to divide and turn into new neurons in specific brain regions. The function of these neuroprogenitor cells remains an intense area of research. Scientists at the National Institutes of Health (NIH) report that newly formed brain cells in the mouse olfactory system — the area that processes smells — play a critical role in maintaining proper connections. The results were published in the October 8 issue of the Journal of Neuroscience. 
“This is a surprising new role for brain stem cells and changes the way we view them,” said Leonardo Belluscio, Ph.D., a scientist at NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and lead author of the study.
The olfactory bulb is located in the front of the brain and receives information directly from the nose about odors in the environment. Neurons in the olfactory bulb sort that information and relay the signals to the rest of the brain, at which point we become aware of the smells we are experiencing. Olfactory loss is often an early symptom in a variety of neurological disorders, including Alzheimer’s and Parkinson’s diseases.

In a process known as neurogenesis, adult-born neuroprogenitor cells are generated in the subventricular zone deep in the brain and migrate to the olfactory bulb where they assume their final positions. Once in place, they form connections with existing cells and are incorporated into the circuitry.
Dr. Belluscio, who studies the olfactory system, teamed up with Heather Cameron, Ph.D., a neurogenesis researcher at the NIH’s National Institute of Mental Health, to better understand how the continuous addition of new neurons influences the circuit organization of the olfactory bulb. Using two types of specially engineered mice, they were able to specifically target and eliminate the stem cells that give rise to these new neurons in adults, while leaving other olfactory bulb cells intact. This level of specificity had not been achieved previously.    
In the first set of mouse experiments, Dr. Belluscio’s team first disrupted the organization of olfactory bulb circuits by temporarily plugging a nostril in the animals, to block olfactory sensory information from entering the brain. His lab previously showed that this form of sensory deprivation causes certain projections within the olfactory bulb to dramatically spread out and lose the precise pattern of connections that show under normal conditions. These studies also showed that this widespread disrupted circuitry could re-organize itself and restore its original precision once the sensory deprivation was reversed.
However, in the current study, Dr. Belluscio’s lab reveals that once the nose is unblocked, if new neurons are prevented from forming and entering the olfactory bulb, the circuits remain in disarray. “We found that without the introduction of the new neurons, the system could not recover from its disrupted state,” said Dr. Belluscio.
To further explore this idea, his team also eliminated the formation of adult-born neurons in mice that did not experience sensory deprivation. They found that the olfactory bulb organization began to break down, resembling the pattern seen in animals blocked from receiving sensory information from the nose. And they observed a relationship between the extent of stem cell loss and amount of circuitry disruption, indicating that a greater loss of stem cells led to a larger degree of disorganization in the olfactory bulb.
According to Dr. Belluscio, it is generally assumed that the circuits of the adult brain are quite stable and that introducing new neurons alters the existing circuitry, causing it to re-organize. “However, in this case, the circuitry appears to be inherently unstable requiring a constant supply of new neurons not only to recover its organization following disruption but also to maintain or stabilize its mature structure. It’s actually quite amazing that despite the continuous replacement of cells within this olfactory bulb circuit, under normal circumstances its organization does not change,” he said.
Dr. Belluscio and his colleagues speculate that new neurons in the olfactory bulb may be important to maintain or accommodate the activity-dependent changes in the system, which could help animals adapt to a constantly varying environment.
“It’s very exciting to find that new neurons affect the precise connections between neurons in the olfactory bulb. Because new neurons throughout the brain share many features, it seems likely that neurogenesis in other regions, such as the hippocampus, which is involved in memory, also produce similar changes in connectivity,” said Dr. Cameron.
The underlying basis of the connection between neurological disease and changes in the olfactory system is also unknown but may come from a better understanding of how the sense of smell works. “This is an exciting area of science,” said Dr. Belluscio, “I believe the olfactory system is very sensitive to changes in neural activity and given its connection to other brain regions, it could lend insight into the relationship between olfactory loss and many brain disorders.”
This work was supported by the NIH Intramural Program.
For more information about brain research, please visit http://www.ninds.nih.gov
NINDS is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. 
About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit http://www.nimh.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.


Making “scents” of new cells in the brain’s odor-processing area
Adult-born cells travel through the thin rostral migratory stream before settling into the olfactory bulb, the large structure in the upper right of the image. Courtesy of the Belluscio Lab, NINDS.

Posted: 10/18/2014 4:20:10 PM by Don Margolis | with 0 comments

Are you or a loved one interested in receiving stem cell treatment? For free information, please fill out our treatment form or email me don@repairstemcells.org and just put TREATMENT in the subject box and the MEDICAL CONDITION in the message.
Center for Adult Stem Cell Research and Regenerative Medicine
Our goal for the newly established Center for Adult Stem Cell Research and Regenerative Medicine is to shape and lead in the research, ethics, and societal implications for the field of adult.
Posted: 10/13/2014 4:33:42 PM by Don Margolis | with 0 comments

Are you or a loved one interested in receiving stem cell treatment? For free information, please fill out our treatment form or email me don@repairstemcells.org and just put TREATMENT in the subject box and the MEDICAL CONDITION in the message.
A stroke therapy using stem cells extracted from patients’ bone marrow has shown promising results in the first trial of its kind in humans.
Five patients received the treatment in a pilot study conducted by doctors at Imperial College Healthcare NHS Trust and scientists at Imperial College London.
The therapy was found to be safe, and all the patients showed improvements in clinical measures of disability.
The findings are published in the journal Stem Cells Translational Medicine. It is the first UK human trial of a stem cell treatment for acute stroke to be published.
The therapy uses a type of cell called CD34+ cells, a set of stem cells in the bone marrow that give rise to blood cells and blood vessel lining cells. Previous research has shown that treatment using these cells can significantly improve recovery from stroke in animals. Rather than developing into brain cells themselves, the cells are thought to release chemicals that trigger the growth of new brain tissue and new blood vessels in the area damaged by stroke.

“Our aim is to develop a drug, based on the factors secreted by stem cells, that could be stored in the hospital pharmacy so that it is administered to the patient immediately following the diagnosis of stroke in the emergency room.”

– Professor Nagy Habib
Department of Surgery and Cancer

MRI scans showing brain damage in the stroke patients before treatment. Source: Stem Cells Translational Medicine.

The patients were treated within seven days of a severe stroke, in contrast to several other stem cell trials, most of which have treated patients after six months or later. The Imperial researchers believe early treatment may improve the chances of a better recovery.
A bone marrow sample was taken from each patient. The CD34+ cells were isolated from the sample and then infused into an artery that supplies the brain. No previous trial has selectively used CD34+ cells, so early after the stroke, until now.
Although the trial was mainly designed to assess the safety and tolerability of the treatment, the patients all showed improvements in their condition in clinical tests over a six-month follow-up period.
Four out of five patients had the most severe type of stroke: only four per cent of people who experience this kind of stroke are expected to be alive and independent six months later. In the trial, all four of these patients were alive and three were independent after six months.
Dr Soma Banerjee, a lead author and Consultant in Stroke Medicine at Imperial College Healthcare NHS Trust, said: “This study showed that the treatment appears to be safe and that it’s feasible to treat patients early when they might be more likely to benefit. The improvements we saw in these patients are very encouraging, but it’s too early to draw definitive conclusions about the effectiveness of the therapy. We need to do more tests to work out the best dose and timescale for treatment before starting larger trials.”
Over 150,000 people have a stroke in England every year. Survivors can be affected by a wide range of mental and physical symptoms, and many never recover their independence.
Stem cell therapy is seen as an exciting new potential avenue of treatment for stroke, but its exact role is yet to be clearly defined.
Dr Paul Bentley, also a lead author of the study, from the Department of Medicine at Imperial College London, said: “This is the first trial to isolate stem cells from human bone marrow and inject them directly into the damaged brain area using keyhole techniques. Our group are currently looking at new brain scanning techniques to monitor the effects of cells once they have been injected.”
Professor Nagy Habib, Principal Investigator of the study, from theDepartment of Surgery and Cancer at Imperial College London, said: “These are early but exciting data worth pursuing. Scientific evidence from our lab further supports the clinical findings and our aim is to develop a drug, based on the factors secreted by stem cells, that could be stored in the hospital pharmacy so that it is administered to the patient immediately following the diagnosis of stroke in the emergency room. This may diminish the minimum time to therapy and therefore optimise outcome. Now the hard work starts to raise funds for this exciting research.”
The study was funded by OmniCyte Ltd and the National Institute for Health Research Imperial Biomedical Research Centre.

Posted: 10/10/2014 4:25:28 PM by Don Margolis | with 0 comments

Are you or a loved one interested in receiving stem cell treatment? For free information, please fill out our treatment form or email me don@repairstemcells.org and just put TREATMENT in the subject box and the MEDICAL CONDITION in the message.
After more than 20 years of research, a team of scientists are bioengineering penises in the lab which may soon be transplanted safely on to patients. It is an extraordinary medical endeavour that has implications for a wide range of disorders.


Dr Anthony Atala: ‘We were completely stuck. We had no idea how to make this structure, let alone make it so it would perform like the natural organ.’

Gathered around an enclosure at the Wake Forest Institute for Regenerative Medicine in North Carolina in 2008, Anthony Atala and his colleagues watched anxiously to see if two rabbits would have sex. The suspense was short-lived: within a minute of being put together, the male mounted the female and successfully mated.
While it’s not clear what the rabbits made of the moment, for Atala it was definitely special. It was proof that a concept he’d been working on since 1992 – that penises could be grown in a laboratory and transplanted to humans – was theoretically possible. The male rabbit was one of 12 for which he had bioengineered a penis; all tried to mate; in eight there was proof of ejaculation; four went on to produce offspring.

The media’s coverage of Atala’s announcement a year later was understandably excited. Not just because of the novelty of a man growing penises in a laboratory, but because his work would fulfil a real need for men who have lost their penis through genital defects, traumatic injury, surgery for aggressive penile cancer, or even jilted lovers exacting revenge.
At present, the only treatment option for these men is to have a penis constructed with skin and muscle from their thigh or forearm. Sexual function can be restored with a penile prosthetic placed inside. The prosthetics can be either malleable rods, with the penis left in a permanently semi-rigid state and thus difficult to conceal, or inflatable rods, which have a saline pump housed in the scrotum. Both technologies have been around since the 1970s. The aesthetics are crude and penetration is awkward.
Another option is a penis transplant from another individual, but this carries a risk of immunological rejection. The chance of organ death can be lessened with anti-rejection drugs, but these drugs have serious side-effects. Transplants can also have a psychological impact, especially with an organ as intimate as the penis. In 2006, a Chinese man was the first to receive a donor penis; two weeks after the 15-hour operation, surgeons removed the transplanted organ on the request of both the patient and his partner.

Atala hopes his technique will mitigate both immunological and psychological issues because his penises would be engineered using a patient’s own cells. “The phallus is actually much longer than you think,” he explains. “It goes all the way behind the pelvis, so no matter the extent of the damage, there is a high probability that there are salvageable cells.”
Peruvian-born Atala, a urological surgeon and professor of regenerative medicine, heads a 300-strong team at the institute. He corrects himself constantly, always going back to edit his speech, adding words such as “high probability“ or “in all likelihood” to be sure his sentences are word-perfect. Soft-spoken and mild-mannered, Atala is a trailblazer in the field and you can’t help but think that his measured speech is an attempt to provide a sure path for others to follow.
To some, engineering human organs sounds like science fiction, but for Atala it’s an absolute necessity. As we live longer (and thus our organs fail more) the shortage of organs for donation will only get worse. If he can work out how to generate the organs people need in a reliable and effective way, the technology can improve a lot of people’s lives. In 2006, Atala and his team announced the first successful bioengineered organ transplant, a bladder, which had been implanted into seven patients in 1999. Earlier this year he announced the successful follow-up of four women given bioengineered vaginas in 2005-2008. Despite these successes, he says, the penis is proving trickier.
Organs increase in architectural complexity as they go from flat structures such as skin, cylindrical structures such as the vagina, to hollow non-tubular organs such as the bladder. As a solid organ, the penis tops this list in both density of cells and structural complexity. It consists of a spongy erectile tissue unique to it. During an erection, signals from the nerves trigger blood vessels to dilate, filling this spongy tissue with blood and causing the penis to lengthen and stiffen.
“We were completely stuck,” says Atala of the first few years of research in the early 90s. “Even the idea of the field of regenerative medicine was brand new at the time. We had no idea how to make this structure, let alone make it so it would perform like the natural organ.” Then, in 1994, he figured he could take a helping hand from Mother Nature. Using a technique pioneered for biological skin dressings, he would take a donor penis and soak it in a mild detergent of enzymes for a couple of weeks to wash away the donor cells.
“You’re left with a mostly collagen scaffold – a skeleton if you like, that looks and feels just like the organ,” explains James Yoo, one of Atala’s collaborators at the institute. “Think of it like a building. If you remove all the furniture and the people, you’re still left with the main structure of the building. Then you replace the tenants with new ones. That’s the whole idea. It’s just that the building is a penis and the tenants are cells.”
The next step is to reseed the structure with the patient’s own cells taken in a biopsy from salvageable tissue and grown in culture. Smooth muscle cells, which relax during an erection to allow the vessels to dilate and the penis to fill with blood, are first, followed by endothelial cells which line the interior surface of blood and lymphatic vessels. When ready, the bioengineered penis is ready to be transplanted to the recipient.
So why, six years on from successfully engineering a penis for rabbits, have they not yet done the same for humans? Atala explains that, as is often the case with these things, scaling up is proving difficult. “Even though we can make them in a very small mammal, we have to tweak the technology, the processes, the ratio of cells and so on, to get larger and larger structures. That’s pretty much what we’ve been doing since the rabbits.”
They’ve made encouraging progress. Atala has engineered half a dozen human penises. Although they are not yet ready for transplanting, Atala’s team are assessing the structures for safety and effectiveness. One machine squashes, stretches and twists them to make sure they can stand up to the wear of everyday life; another pumps fluid into them to test erections. Sliced segments are tested at the genetic, cellular and physiological level.
“It’s a rigorous testing schedule,” says Atala, wearily. “But we’re trying to get approval from the US Food and Drug Administration so we know everything is perfect before we move to a first in-man test.”
Neither Atala nor Yoo will be pushed for a date for the first test in man, saying only that they’d expect it to occur within five years. “In the end we’re aiming for the entire size of the organ,” says Atala. “But in reality our first target is going to be partial replacement of the organ.”
In the short term, this would include growing smaller lengths for partially damaged penises, but would also include replacing parts of the penis to help cure erectile dysfunction. Degradation of the spongy erectile tissue, says Tom Lue, a urological surgeon at the University of California, San Francisco, is the leading cause of impotence in old age. Disorders such as high blood pressure or diabetes can damage the delicate tissue – the resulting scar tissue is less elastic, meaning the tissue cannot completely fill with blood and the penis cannot become fully erect.
“Show me a hundred 70-year-old men with erectile dysfunction,” says Lue, “and I’ll bet you 90% of them have scar material in their penis.” Traumatic injury or priapism, a condition that leaves men with an increasingly painful erection for hours or even days, can also damage the tissue and cause erectile dysfunction in younger men. “If you replace the damaged spongy tissue you can give these men a better erection.”
Engineering the spongy tissue for replacement is one of Atala and Yoo’s interim goals. Lue is also hoping to restore erections, but for less severely damaged penises. For instance, some men become impotent after surgery for prostate or rectal cancer because the nerves that regulate erections, which run through the rectum and prostate into the centre of the penis, can get damaged. Likewise with traumatic injury, if the vessels are severed then the penis cannot fill with blood.
Microsurgery to connect the vessels and nerves in the penis is possible but often ineffective. Lue is testing whether injecting stem cells into the base of the penis can encourage the nerves and cells to rejoin. His work might also help Atala and Yoo to stimulate nerve and vessel regrowth when the day comes for the first in-man trial of a bioengineered penis. Twenty-two years into his research to bioengineer a human penis, Atala is a man who is both excited and impatient for that day. And you’d suspect he’s not the only one.

Bioengineered organs: The story so far…

In 1999 the bladder became the first laboratory-grown organ to be given to a human. Atala and his colleagues took cells from a biopsy from seven patients with bladder disease. The cells were cultured and then seeded, layer by layer, on to a biodegradable, bladder-shaped collagen scaffold. After about eight weeks they were transplanted to patients, where the organs developed and integrated into the body.
Another pilot study, this time in four women with a rare congenital abnormality that causes the vagina and uterus to be underdeveloped or absent. Using a similar technique to the one used to make bladders, in 2005 they implanted the first vagina. Up to eight years after transplant, all four organs have normal structure and function. This technique could be used to help women following injury or cancer.
Penis and beyond
In 2004, they implanted the first bioengineered urethra into five boys. This technology will help in their work towards reconstructing the penis. Atala and his colleagues are also working on 30 different organs and tissues including a kidney, which could be made using a 3D printer, and tissue for the liver, heart and lung.

Posted: 10/8/2014 11:09:10 AM by Don Margolis | with 0 comments

Are you or a loved one interested in receiving stem cell treatment? For free information, please fill out our treatment form or email me don@repairstemcells.org and just put TREATMENT in the subject box and the MEDICAL CONDITION in the message.
Israel's BrainStorm Cell Therapeutics said the U.S. Food and Drug Administration has designated its adult stem cell treatment as a "fast-track" product for the treatment of amyotrophic lateral sclerosis (ALS).

BrainStorm's treatment, called NurOwn, is being studied in a mid-stage clinical trial in patients with ALS, also known as Lou Gehrig's Disease.
The FDA's fast track program is designed to speed up access to drugs intended to treat serious conditions and which have the potential to address unmet medical needs.
"The receipt of fast-track designation from the FDA is an acknowledgement of the unmet medical need in ALS," BrainStorm Chief Executive Tony Fiorino said on Tuesday.
"What is so valuable about fast track designation to a small company like BrainStorm is the opportunity to have increased meetings with and more frequent written communication from the FDA," he said, adding that only a small number of cellular therapies have received FDA approval.
BrainStorm said the last patient has completed the last visit in its phase 2a clinical trial in ALS at Hadassah Medical Center in Jerusalem. The company expects to release final results of the study in the fourth quarter of 2014.
NurOwn is also being studied in a phase 2 clinical trial at three sites in the United States.
According to the ALS Association, 5,600 people in the United States are diagnosed each year with the disease, which has severely disabled British physicist Stephen Hawking.
Posted: 10/7/2014 11:06:00 AM by Don Margolis | with 0 comments

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