A DRUG that stops the body from rejecting bone marrow transplants in cancer patients could be ready for human trials in three years time.

The latest development comes after more than a decade of research unlocking the function of a protein called perforin, which kills rogue cells in the body.

Australian researchers involved in unravelling perforin's molecular structure, a discovery published in the journal Nature in 2010, are now working towards developing a safe drug to block the protein.

Perforin plays a key role in the body's immune response by punching holes in, and killing, cells which have been hijacked by viruses or cancer to rid the body of disease.

However, the protein is problematic for bone marrow transplant patients because it can cause the body to reject the treatment.

For this reason, a project led by the Peter MacCallum Cancer Centre in Melbourne is developing a drug to inhibit the protein in bone marrow stem cell transplant patients to help their recovery.

The drug works in mouse models, but a $6.8 million grant from the UK's Wellcome Trust will allow the drug to be fine-tuned for human trials.

"In the mouse models we use, we know the inhibitors are effective," project leader Professor Joe Trapani, executive director of cancer research at Peter Mac, told AAP.

"They actually help stem cells survive when they would otherwise be rejected."

The Peter Mac team is working with New Zealand chemist Prof Bill Denny to refine the drug, along with Monash University and Queensland Institute of Medical Research scientists.

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Bone marrow transplant drug a step closer

Public release date: 4-Jun-2012 [ | E-mail | Share ]

Contact: David Eve Celltransplantation@gmail.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Tampa, Fla. (June 4, 2012) When autologous (self-donated) lung-derived mensenchymal stem cells (LMSCs) were transplanted endoscopically into 13 adult female sheep modeled with emphysema, post-transplant evaluation showed evidence of tissue regeneration with increased blood perfusion and extra cellular matrix content. Researchers concluded that their approach could represent a practical alternative to conventional stem cell-based therapy for treating emphysema.

The study is published in Cell Transplantation (21:1), now freely available on-line at http://www.ingentaconnect.com/content/cog/ct/.

"Mensenchymal stem cells are considered for transplantation because they are readily available, highly proliferative and display multi-lineage potential," said study corresponding author Dr. Edward P. Ingenito of the Brigham and Women's Hospital Division of Pulmonary and Critical Care Medicine. "Although MSCs have been isolated from various adult tissues - including fat, liver and lung tissues - cells derived from bone marrow (BM) have therapeutic utility and may be useful in treating advanced lung diseases, such as emphysema."

However, according to the authors, previous transplantation studies, many of which used an intravenous delivery method, have shown that BM-MSCs have been only marginally successful in treating lung diseases. Further, therapeutic responses in those studies have been limited to animal models of inflammatory lung diseases, such as asthma and acute lung injury.

To try and answer the questions surrounding the utility of BM-MSCs for treating advanced emphysema, a disease characterized by tissue destruction and loss of lung structural integrity, for this study the researchers isolated highly proliferative, mensenchymal cells from adult lung parenchyma (functional tissue) (LMSCs) and used an endoscopic delivery system coupled with a scaffold comprised of natural extracellular matrix components.

"LMSCs display efficient retention in the lung when delivered endobronchially and have regenerative capacity through expression of basement membrane proteins and growth factors," explained Dr. Ingenito.

However, despite the use of autologous cells, only a fraction of the LMSCs delivered to the lungs alveolar compartment appeared to engraft. Cell death likely occurred because of the failure of LMSCs to home to and bind within their niche, perhaps because the niche was modified by inflammation or fibrosis. These cells are attachment-dependent and failure to attach results in cell death."

Their findings did suggest, however, that LMSCs were capable of contributing to lung remodeling leading to documented functional improvement rather than scarring 28 days post transplantation.

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Cell transplantation of lung stem cells has beneficial impact for emphysema

PITTSBURGH (KDKA) Injecting stem cells into the brain of someone who has had a stroke is a hot button issue.

Is it safe? Can it be done?

Thats what researchers at the University of Pittsburgh are trying to find out.

Because these are cells that have not been injected into the brain before, we need to know whether it is safe to do so, UPMC neurologist Dr. Lawrence Wechsler said.

So far, at UPMC, two people have received injections of stem cells from the bone marrow of healthy adult donors.

Roger Hill is one of them.

In August 2009, he woke up with a stroke. The first thing he noticed was his vision. He couldnt see half of his world and then his left side left him.

Something happened with my left leg. I fell down, he said. I couldnt feel my left knee.

The problem was in the brain.

A stroke most commonly happens because of a blocked artery. Part of the brain dies from a lack of oxygen and blood flow. Stroke is a leading cause of death and disability.

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Researchers Testing Stem Cells As Treatment For Stroke Recovery

SOUTHAMPTON, England, June 3 (UPI) -- British physicians say some patients with osteonecrosis who need hip replacements could be treated with stem cells from their own bone marrow.

The procedure, developed by Doug Dunlop of Southampton General Hospital in England, involves mixing the stem cells with cleaned, crushed bone from another patient who has had his own hip replaced and using it to fill the hole made after damaged tissue removed from the joint, The Daily Telegraph reported.

The new stem cell therapy could prevent the need for hip replacements due to osteonecrosis, a condition where poor blood supply causes significant bone damage leading to severe arthritis, Dunlop said.

The stem cells send chemical signals to blood vessels and it's hoped the new vessels in the hip would supply nutrients to improve bone strength, Dunlop explained.

Oesteoarthrits, caused by wear and tear of the bone, results from the temporary or permanent loss of blood flow to bones.

This causes osteonecrosis -- or the bones to "die" -- and ultimately severe arthritis, but if osteonecrosis occurs at the bone joint, it can cause it to collapse and the only option is a hip replacement, Dunlop said.

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Stem cells may preclude hip replacements

Research scientist Dr Paul Turner (left) and cell biologist Dr Jim Faed examine bone marrow stem cell colonies in the Spinal Cord Society Research Laboratory in Dunedin. Photo by Gerard O'Brien.

University of Otago cell biologist, haematologist and project leader Dr Jim Faed said $1.4 million was needed to trial the use of bone marrow stem cells to stimulate insulin production in type 1 diabetics.

Fundraising is being co-ordinated by the Spinal Cord Society, which had started recruiting for a related trial for spinal cord injury sufferers, to be led by Dr Faed.

That trial, which would have used cells from the person's nose, is on hold, partly for lack of funds, and partly because the diabetes trial would lay the groundwork for better-designed spinal cord research.

The diabetes study would be carried out in the Spinal Cord Society Research Laboratory at Otago University's Centre for Innovation in Dunedin, taking about two years.

Dr Faed said recent research from the United States had "electrified" interest in using stem cells to treat type 1 diabetics.

In what is known as the Chicago study, umbilical cord stem cells were shown to increase insulin production in even the most severe diabetics.

Dr Faed said he hoped the Dunedin study, with a dozen participants, would replicate and expand the Chicago study by explaining the mechanism by which the stem cells promoted insulin production.

Pharmaceutical companies stood to make no money from stem cell research, as the product was generated by the patient's own body; thus the companies could not be tapped for funds.

Dr Faed acknowledged the disappointment of the several spinal cord injury sufferers who had to wait longer for their study.

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Researchers appealing to public for funds

In 2004, I had been stationed at Aviano Air Base, Italy, for about a year. One day, while walking into the base exchange, I was approached by an individual standing by one of the many tables that we associate with trying to sell us something or peddle information.

This person was just like you and I, another military member, but the difference was that he had volunteered to try and convince us (Jane and Joe Public) to sign up to potentially help a leukemia patient by donating bone marrow or peripheral blood stem cells.

I was not opposed to the thought of being a registered donor, and in fact signed up that very day. The process only took 10 minutes to fill out the paperwork, and four swabs of the inside of my mouth for molecular matching of donor to recipient. Later I thought, probably like many people before me, What are the chances I will ever be called on to donate?

Next thing I knew it was 2008. I was in my office working on some building project updates, and planning to take some leave, when I received an email from some guy I didnt know. It was a strange name along with a strange email address. I thought to myself this has to be spam. Then I noticed the email was signed and encrypted, so I went ahead and opened it.

What I read next was both exciting and scary at the same time. Im paraphrasing here, but the email basically stated, Sgt Faulkwell, you have been identified as a potential donor for a leukemia patient. Please respond if you are still willing to donate.

Several weeks, and a few vials of blood later, I was identified as the most appropriate donor for my recipient. My trip was organized and paid for by the recipients insurance. They explained that I could have had a friend or family member come with me, or travel from anywhere else in the world to meet me and stay for the whole donation period. It is definitely not something that someone has to go through alone.

In the end, I was asked to donate stem cells. The process took five days, in which I received two shots every day to boost my blood stem-cell production. Essentially, I was mass producing blood stem cells, which are neither red nor white cells yet. The cells were harvested on the fifth day.

It was a fairly painless process, but is highly dependent on each individuals own body composition, health, etc. Stem-cell harvesting is similar to having a transfusion. They pull your blood out, spin it in a machine to withdrawal the stem cells, and then return your blood to you. There were some minor side effects, but nothing compared to what my recipient must have been going through.

My donation went extremely well, and I found out roughly one year later that my recipient had graphed with my stem cells, and that he was doing better. I never received another update, but I hope one day to get the chance to meet the person.

There are too many myths and facts out there for me to get into, but the next time you have someone approach you to become a registered bone-marrow donor, I hope you will take the time to register. You could very well save someones life!

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Are you a bone-marrow donor? You could save someone’s life today

A gravely ill Tucson teen is hoping a bone-marrow drive this weekend will give her a new chance at life.

Delia Gonzalez was diagnosed with a rare blood disorder called aplastic anemia three years ago. While medication kept the illness at bay for a while, she's now surviving on blood transfusions to keep her alive and is extremely sick, family friend Laine Sklar said.

Aplastic anemia occurs when the body's bone marrow doesn't make enough new blood cells. Bone marrow is a spongelike tissue inside the bones. It makes stem cells that develop into red blood cells, white blood cells and platelets.

Gonzalez, 19, who is Hispanic and Norwegian, needs a bone-marrow transplant to save her life but has not been able to find a match among her close friends and family.

The former Catalina Foothills High School student is hoping to both grow the bone-marrow database and find a match for herself, Sklar said.

The bone-marrow drive will be held at two locations from 8 a.m. to 1 p.m. this Sunday. Southern Arizonans between the ages of 18 and 60 are invited to give a cheek swab at Most Holy Trinity Catholic Church, 1300 N. Greasewood Road, and at Ramada 7 in Reid Park across from the McDonald's on East 22nd Street.

Donors with diverse racial or ethnic backgrounds are especially critical, as patients in need of a transplant are most likely to match someone of their own race and ethnicity.

Patients particularly need potential donors between the ages of 18 and 44. That's because younger donors produce more and higher-quality cells than older donors.

All cheek swabs will become part of the Be the Match Registry to potentially help thousands of patients with life-threatening diseases.

The National Marrow Donor Program operates the Be the Match Registry and partners with a global network of leading hospitals, cord-blood banks, laboratories and recruiters.

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Bone-marrow drive on Sunday aims to help sick Tucson teen

Health

May 30, 2012

by Suzanne Kurtz, JTA

For nearly a year, Julie Gavrilov has been trying to find a match for her father, Mark.

Diagnosed with a rare and aggressive blood cancer, he needs a stem cell transplant to survive the disease.

A Bukharian Jew born in Uzbekistan, he will have the best chance of survival if he finds a donor from within his own ethnic community.

Since learning of her 58-year-old fathers diagnosis, Gavrilov, an attorney in New York, has organized a donor drive at a Bukharian Jewish community center in the Queens borough of the city, written heartfelt messages for local synagogue newsletters and posted her plea on Facebook.

A compatible donor has yet to be identified, but Gavrilov, 32, is hopeful that the person who can save her fathers life will be found.

It just takes one person, she said.

Finding that person for Jews of non-Ashkenazi descent can be especially difficult.

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Israeli, U.S. drives aiming to increase number of non-Ashkenazi bone marrow donors

LITTLE ROCK, Ark. (KTHV) - There are two ways to donate bone marrow. The method used depends on the patient and is determined by their doctor. It's easier than ever and one volunteer is making sure that message is told.

It's a touching story, a young woman finds out she has leukemia, her long time friend sets out to help find a match to save her life.

The woman is Leslie Harris, now mother to a healthy baby boy, born theday doctors diagnosed her.Her future is still unsure. After three rounds of chemo, she's waiting for a bone marrow match.

He's not a student, but Colin Hall carries his backpack with him everywhere. Inside: his swabbing kits used to find a potential bone marrow donor for his friend Leslie Harris.

GetSwabbed.orgis out to "defeat blood cancer by empowering people to take action, give bone marrow and save lives." Hall is a volunteer rep for the DKMS organization.

Hall says, "Once I found out about [Leslie's leukemia]I got online to send out for MY free bone marrow kit because she needed a bone marrow transplant."

That urgent and emotional response was just the beginning of Hall's involvement in bone marrow donation work. He says the statistics are daunting, "Only 1 in 20,000 people become a match for somebody. And part of the problem is there is only 2 percentof the population on the registry. So we need to get more people on that registry so more people have a chance of finding a match."

While finding a match for the patient is hard enough, add to that the fact that many qualified donors don't know how easy the process can actually be.

Dr. Steve Medlin, with the Myeloma Institute at UAMS, says technology has come a long way in just a few short years.

"This used to be a painful procedure -or a more difficult procedure anyway-in which we'd have to extract the stem cells from the bone marrow typically from the hip bones. Now it's a much more simple procedure...and much better tolerated. It's just a process that takes maybe an hour or so to get the cathater in and maybe 4 to 6 hours on a machine to collect the stem cells then the cathater's out and the process is finished." says Medlin.

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Bone marrow donation easier than ever

Hip replacements for some patients could be a thing of the past after surgeons pioneered a new stem cell procedure to tackle a bone disease that leads to arthritis.

Doctors at Southampton General Hospital are extracting stem cells from the bone marrow of patients in need of hip repair due to osteonecrosis - a condition where poor blood supply causes significant bone damage leading to severe arthritis.

These cells are mixed with cleaned, crushed bone from another patient who has had their own hip replaced and used to fill the hole made by surgeons after dead and damaged tissue has been removed from the joint.

The procedure has been developed by Doug Dunlop, a consultant orthopaedic surgeon at Southampton General Hospital, and Professor Richard Oreffo, a specialist in musculoskeletal science at the University of Southampton.

"Although this work is still ongoing, several patients who have had the procedure have reacted very well and, if we get the results we are hoping for, these patients won't need to have their hip joints replaced - they should be fixed completely," said Mr Dunlop.

Professor Oreffo added: "By using stem cells to send out chemical signals to blood vessels, we hope the body will continue to create new vessels in the hip which supply enough nutrients to maintain bone strength."

Osteonecrosis is on the rise in the UK with around 4,000 cases a year but it is much more widespread in Asia where it is the most common form of arthritis of the hip, the hospital said.

It can also be treated with drugs to help avoid arthritis and usually strikes between 30 and 50 years of age.

Osteonecrosis is one of the three main causes of arthritis alongside osteoarthritis and rheumatoid arthritis.

Arthritis in general affects one in five people in the UK.

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Stem cell hope for hip replacement procedure

For Jonathan Provost, choosing his Eagle Scout project was an easy choice. Jonathan's cousin, Matthew Zieman, passed away from Acute Lymphatic Leukemia in February at the age of 24. Because of this, Jonathan's Eagle Scout project is a bone marrow donor registry drive.

"Matt was at his apartment last year and noticed a few bumps on the back of his neck," Jonathan said. "He just ignored them for a few weeks and then he told one of his friends, and she said to get it checked out. So he went by the hospital, they did a few tests, and they found out it was leukemia."

Jonathan hopes the drive will find a number of donors who can help current cancer patients, due to the difficulty of finding donor matches. Immediate family members are generally the first place doctors look for bone marrow donors; Matthew's only sibling wasn't a match, however, which made finding a donor more difficult.

The drive will be held from noon to 4 p.m. on Saturday, June 9, at Brad Duren Dentistry, located at 4030 Justin Road, Suite 102, in Flower Mound. The office is past the Chinn Chapel Soccer Complex and across from the Crossroads Bible Church. Jonathan chose the office partly because of its location and partly because of a familiarity.

"It's also off a popular road, and [Brad] told me he'd let me host the donor drive for free," he said. "He's my dentist and my mom works here, too."

The process of becoming a donor is easy. After having a cheek swab done, potential donors merely have to fill out a donor consent form, which will place them in the national bone marrow donor registry. Testing is then done to determine a genetic match between cancer patients and their potential donor. Patients see better results the closer a donor's genetics match his or her own.

If an individual is chosen as a blood donor, he or she will be called to Carter BloodCare to donate blood.

"A lot of people don't know it's really easy to do this -- it's not a complicated process at all," Jonathan said. "They generally don't put a needle in your hip anymore; they normally just take blood and that's it. The process is a lot simpler than it used to be."

Following a successful blood donation, known as peripheral blood stem cell donation, doctors will obtain stem cells from the blood of the donor. Those stem cells will then be given to a cancer patient that's a genetic and blood match in order to stimulate healthy red blood cell production.

If a donor is selected to give a bone marrow donation, he or she will have liquid marrow extracted from the back of the pelvic bone. This type of donation is far less likely, however.

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Flower Mound boy hopes to add bone marrow donors: Jonathan Provost's Eagle Scout project could help save lives

Photo by Rachel Denny Clow, Corpus Christi Caller-Times // Buy this photo

Rachel Denny Clow/Caller-Times Cristina Rodriguez sits with her dogs Coby (left) and Flower at her home Thursday. Rodriguez, who has non-Hodgkin lymphoma, is having a Zumba benefit on Sunday and inviting people to register to donate bone marrow. Rodriguez is a former Zumba instructor.

CORPUS CHRISTI Had Cristina Rodriguez's cancer been more aggressive, had it penetrated her bones, things might have been different.

And while she has had chemotherapy, she has lost her hair and needs a stem cell treatment, but she doesn't need a bone-marrow transplant.

And for that, she's lucky.

Hispanics needing bone marrow have a harder time finding matching donors than do other ethnicities because few Hispanics have registered to donate.

"That could've easily been me," Rodriguez said.

That's why Rodriguez, 31, is trying to raise awareness about the importance for Hispanics to give bone marrow. The former Zumba instructor is hosting a Zumba event Sunday afternoon that partly is a fundraiser for her ongoing cancer treatments and partly a campaign to encourage more people to become donors.

Among the 8 million people signed up as bone marrow donors, 800,000 or 10 percent, identify themselves as Hispanic or Latino. Though Hispanics comprise more than one-third of Texas' population, only 17 percent of registered bone marrow donors in the state are Hispanic.

Overall, Hispanics have a 72 percent chance of finding a bone marrow donor, compared with whites, who have a 93 percent chance, according to the donor program. Only blacks fare worse, with a 63 percent likelihood of finding a donor.

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Former Zumba instructor with cancer encourages Hispanics to donate bone marrow

Editor's Choice Main Category: Multiple Sclerosis Article Date: 24 May 2012 - 14:00 PDT

Current ratings for: 'Recovery From Multiple Sclerosis By Growth Factor In Stem Cells'

4.7 (10 votes)

4.5 (2 votes)

Animals that were injected with hepatocyte growth factor were noted to have grown new neural cells and lower levels of inflammation. Most significantly, the researchers noted that the protective envelope of myelin, the myelin sheath, which surrounds the core of a nerve fiber and facilitates the transmission of nerve impulses, re-grew and covered lesions that were caused by MS.

Robert H. Miller, professor of neurosciences at the School of Medicine and vice president for research at Case Western Reserve University declared: "The importance of this work is we think we've identified the driver of the recovery."

MS is caused by damage to the myelin sheath, the protective covering that surrounds nerve cells. The nerve damage is caused by inflammation, which occurs when the body's own immune cells attacks the nervous systems located in areas of the brain, the optic nerve, and spinal cord. This damage can cause an interruption of the nerve signals, which results in loss of balance and coordination, cognitive ability, as well as in other functions and in time, these intermittent losses may become permanent. In 2009, Caplan and Miller discovered that mice with MS injected with human mesenchymal stem cells recovered from the type of damage that was brought on by MS. A clinical trial is currently underway based on their research, whereby patients with MS are injected with their own stems cells.

During this trial, the team decided to first establish whether the presence of stem cells or other cells induce recovery. They injected a total of 11 animals with MS with the medium, in which mesenchymal stem cells that were taken from bone marrow grew, discovering that all animals displayed a rapid reduction in functional deficits. An analysis demonstrated that unless the injected molecules had a certain size or weight, i.e. between 50 and 100 kiloDaltons, the course of the disease remained unchanged.

Other research, as well as the team's own studies, suggested that this was likely to be instigated by the hepatocyte growth factor, which is secreted by mesenchymal stem cells.

The team then injected the animals with either 50 or 100 nanograms of the growth factor on alternate days for a 5-day period and observed a decrease in the level of signaling molecules that promote inflammation, whilst the level of signaling molecules that oppose inflammation increased. The researchers noted a growth of neural cells, whilst nerves that were exposed because of MS were rewrapped with myelin. Recovery was marginally better in those mice that received the 100-nanogram injections compared with those receiving the 50-nanogram injections.

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Recovery From Multiple Sclerosis By Growth Factor In Stem Cells

A growth factor isolated from human stem cells shows promising results in a mouse model of multiple sclerosis.

Human mesenchymal stem cells (hMSCs) have become a popular potential therapy for numerous autoimmune and neurological disorders. But while these bone marrow-derived stem cells have been studied in great detail in the dish, scientists know little about how they modulate the immune system and promote tissue repair in living organisms.

Now, one research team has uncovered a molecular mechanism by which hMSCs promote recovery in a mouse model of multiple sclerosis (MS).

According to research, published online Sunday (May 20) in Nature Neuroscience, a growth factor produced by hMSCs fights MS in two ways: blocking a destructive autoimmune response and repairing neuronal damage. The finding could help advance ongoing clinical trials testing hMSCs as a therapy for MS.

The researchers have identified a unique factor that has surprisingly potent activity mediating neuron repair, said Jacques Galipeau, a cell therapy researcher at Emory University in Atlanta, Georgia, who was not involved in the research. The magnitude of the effect on a mouse model of MS is a big deal.

MS is an autoimmune disease in which the immune system attacks myelin sheaths that surround and protect nerve cells. The attack leaves nerves exposed and unable to send signals to the brain and back, resulting in the loss of motor skills, coordination, vision, and cognitive abilities. There is no cure for MS, and most current therapies work to simply suppress the immune system, preventing further neuronal damage. None have demonstrated an ability to also repair damaged myelin and promote recovery.

In 2009, Robert Miller and colleagues at Case Western Reserve University in Cleveland, Ohio, demonstrated that hMSCs dramatically reversed the symptoms of multiple sclerosis in a mouse model of the disorder. The animals got better, recalled Miller. The team hypothesized that the stem cells suppress the immune response and promote remyelination.

But Miller wanted to know exactly what the cells were doing. To find out, his team isolated the medium on which the hMSCs were grown to determine if the cells or something they secreted was responsible for the observed recovery. The medium alone was enough to induce recovery in mice, pointing to the latter.

To find out exactly which molecule or molecules in the medium were responsible, the researchers separated the proteins in the fluid based on the molecular weight and injected each isolate into mice exhibiting symptoms of MS. The mid-weight solution, of proteins with masses between 50 and 100 kilodaltons (kDa), caused recovery. That eliminated a huge number of potential candidates, said Miller.

The researchers then narrowed the field again with a literature search for a molecule that fit their criteria: secreted by hMSCs, 50-100 kDa in size, and involved in tissue repair. They identified hepatocyte growth factor (HGF), a cytokine made by mesenchymal cells that has been shown to promote tissue regeneration and cell survival in numerous experiments. Sure enough, HGF alone was enough to promote recovery in the MS mouse models, and blocking the receptor for HGF in those mice blocked recovery. The team also demonstrated that HGF suppresses immune responses in vivo and accelerates remyelination of neurons in vitro. Finally, they saw that HGF causes remyelination in rats with a lesion on their spinal cord.

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Could Stem Cells Cure MS?

On a special surface that could help advance stem cell therapies, UM researchers have turned human skin cells into adult-derived stem cells, coaxed them into bone cells and then transplanted them into holes in the skulls of mice. The cells produced four times as much new bone growth as in the mice without the extra bone cells. In this pink-stained image, the black outline partially encloses the new bone growth in the skull. Image credit: Villa-Diaz, L.G., Brown, S.E., Liu, Y. Ross, A.M., Lahann, J.M., Krebsbach, P.H., University of Michigan

ANN ARBOR University of Michigan researchers have proven that a special surface, free of biological contaminants, allows adult-derived stem cells to thrive and transform into multiple cell types. Their success brings stem cell therapies another step closer.

To prove the cells regenerative powers, bone cells grown on this surface were then transplanted into holes in the skulls of mice, producing four times as much new bone growth as in the mice without the extra bone cells.

An embryos cells really can be anything they want to be when they grow up: organs, nerves, skin, bone, any type of human cell. Adult-derived induced stem cells can do this and better. Because the source cells can come from the patient, they are perfectly compatible for medical treatments.

In order to make them, Paul Krebsbach, professor of biological and materials sciences at the UM School of Dentistry, said, We turn back the clock, in a way. Were taking a specialized adult cell and genetically reprogramming it, so it behaves like a more primitive cell.

Specifically, they turn human skin cells into stem cells. Less than five years after the discovery of this method, researchers still dont know precisely how it works, but the process involves adding proteins that can turn genes on and off to the adult cells.

Before stem cells can be used to make repairs in the body, they must be grown and directed into becoming the desired cell type. Researchers typically use surfaces of animal cells and proteins for stem cell habitats, but these gels are expensive to make, and batches vary depending on the individual animal.

You dont really know whats in there, said Joerg Lahann associate professor of chemical engineering and biomedical engineering.

For example, he said that human cells are often grown over mouse cells, but they can go a little native, beginning to produce some mouse proteins that may invite an attack by a patients immune system.

The polymer gel created by Lahann and his colleagues in 2010 avoids these problems because researchers are able to control all of the gels ingredients and how they combine.

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UM: Stem-Cell-Growing Surface Enables Bone Repair

May 24, 2012

Connie K. Ho for RedOrbit.com

Technology is rapidly progressing and so is research related to stem cells.

Researchers from the University of Michigan recently announced that they found a special surface without biological contaminants that can help adult-derived stem cells to grow and change into different cell types. The findings, published in the journal Stem Cells, are considered a breakthrough in stem cell research.

In the study, scientists grew bone cells on the surface and then transplanted the cells to the skulls of mice to look at the cells regenerative powers. The results showed that the cells produced four times as much new bone growth in mice without the help of extra bone cells. The importance of these adult-derived induced stem cells is that they come from the patient and these cells are compatible for medical treatments.

We turn back the clock, in a way. Were taking a specialized adult cell and genetically reprogramming it, so it behaves like a more primitive cell, commented Paul Krebsbach, professor of biological and materials sciences at the U-M School of Dentistry, on the process of stem cell creation.

In the project, researchers examined how human skin cells are turned into stem cells and, even though they are not exactly sure as to how the process works, how it involves the addition of proteins that can signal the genes to turn on and off to the adult cells. Prior to being used to repair parts of the body, the stem cells are grown and directed to become a specific cell type. Researchers were able to use the surface of the animal cells and proteins for stem cell habitats, but saw that the amount of cells produced could vary by animal.

You dont really know whats in there, noted Joerg Lahann, associate professor of chemical engineering and biomedical engineering.

One difficulty researchers have encountered in the past is the fact that human cells and animals cells can sometimes mix. However, the polymer gel made by Lahann and his fellow researchers helped avoid this problem. Researchers were able to gain better control over the gels ingredients and how they were combined.

Its basically the ease of a plastic dish, Lahann said. There is no biological contamination that could potentially influence your human stem cells.

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Bone Repair Via Stem-cell-growing Surface

Canadian regulators have approved the world's first stem cell drug.

The drug, Prochymal, will be used to treat a deadly side effect of bone marrow transplants called acute graft-versus host disease (GvHD), which occurs in children.

Acute graft-versus host disease kills about 80 percent of children affected.

Prochymal uses stem cells from healthy adult donors, with one donation able to create 10,000 doses of the drug, reported the New York Times.

The manufacturer, Maryland-based Osiris Therapeutics Inc., saw their shares climb 5.5 percent to $5.55 after losing 24 percent in the last year, reported Bloomberg.

In extended trading, stocks rose 14 percent.

The drug was approved, said Reuters, on the condition that further clinical tests are carried out.

There has been debate about the effectiveness of the drug in recent years.

Late stage clinical trials three years ago failed to show results but more recent tests have shown the drug to be relatively effective about a month into therapy.

Osiris says that it plans to seek approval from the US Food and Drug Administration this year.

Link:
Stem cell drug approved in Canada to treat bone marrow disease

After half a year of blood transfusions to treat life-threatening anemia, 9-year-old Ricky Martinez was running out of time.

The Murrieta boy needed a bone marrow transplant to save his life. Although his parents had held numerous drives seeking a match for their son, the perfect donor eluded them.

Then another option appeared ---- doctors found Ricky's own blood from his umbilical cord, banked at birth, and stored in a medical facility.

"I had donated it at birth, when I delivered," said Ricky's mother, Cynthia Martinez. "I had no idea that I'd be using it for him nine years later."

The cord blood discovery represents a "godsend" for the family, Martinez said, because Ricky's body began rejecting the transfusions that keep him alive.

Cord blood contains stem cells ---- undifferentiated cells that can spur production of healthy tissue to help treat various diseases. Doctors believe it could jump-start Ricky's bone marrow, allowing his body to resume normal blood production.

But it's not a guarantee.

Ricky's condition, aplastic anemia, is an extremely rare disease, and cord blood transplantation is an experimental procedure for the condition, said David Buchbinder, a hematologist and transplant physician who is treating Ricky at Children's Hospital Orange County, in the city of Orange.

Although the procedure offers few risks of complications, it also pushes the boundaries of medical practice, placing Ricky in a realm of mixed medical opinions and uncertain results, Buchbinder said.

His parents say they're willing to go there to save their son's life.

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MURRIETA: Surprise cord-blood find is 'godsend' for ailing boy

Pluristem Therapeutics Ltd. (Nasdaq:PSTI; DAX: PJT: PLTR)has announced that a seven year-old girl suffering from an aplastic bone marrow whose condition was rapidly deteriorating has seen a reversal of her condition. The improvement came due to a significant increase in her red cells, white cells and platelets following the intramuscular injection of Pluristem's PLacental eXpanded (PLX) cells. Aplastic bone marrow is a disease where the patient has no blood-forming hematopoietic stem cells in the bone marrow.

Hadassah Medical Center Bone Marrow Transplantation, Cell Therapy and Transplantation Research Center director Prof. Reuven Or said, "With her body rejecting all possible treatment, and with no other options, we finally turned to Pluristem's PLX cells, which literally saved her life. The results of this unique case indicate that PLX cells may be effective in treating other diseases that affect the bone marrow."

The patient has been hospitalized at the Hadassah Hebrew University Medical Center in Jerusalem since August 2011. Her aplastic bone marrow had been refractory to treatment. So she underwent allogeneic stem cell transplantation from a matched unrelated donor. The first transplant was unsuccessful and the patient remained with bone marrow failure. The patient underwent a second allogeneic stem cell transplantation from a second donor. The bone marrow function was very poor and the patient suffered from recurrent infections.

Two months after the patient's second bone marrow transplant, the child received PLX cells intramuscularly in two doses about one week apart. Some 10 days after the last administration of PLX cells, the patient's hematological parameters began to significantly increase, an effect that has persisted to date. The patient's general clinical status has also improved. Subsequent analysis has indicated that the PLX cells worked by stimulating the recovery of the hematopoietic stem cells contained in the second bone marrow transplant that she had received over two months earlier. Finally, after nine months of hospitalization, the child will be discharged from the hospital.

Pluristem chairman and CEO Zami Alberman said, "Pluristem is extremely happy that our PLX cells have helped this little girl. Remarkably, these beneficial effects were seen in the patient after our PLX cells were administered intramuscularly and correlate with the positive effects on the bone marrow when we administered our PLX cells intramuscularly (IM) in animals exposed to toxic levels of radiation. Pluristem now has several data points to indicate that our PLX cells may work for systemic diseases when given locally, away from the target organ, and without a need to give cells intravenously."

In February 2012, Pluristem announced the results of animal studies suggesting PLX cells can be potentially effective in treating the life threatening hematopoietic complications associated with Acute Radiation Syndrome (ARS). In these experiments, animals given PLX cells IM up to 24 hours post irradiation demonstrated a recovery of their red cells, white cells, platelets and bone marrow to almost normal levels. It was that announcement, and the significant deterioration of the patient following two bone marrow transplants, that led Prof. Or to contact Pluristem about the possible compassionate use of PLX cells to treat his young patient.

Pluristem recently received US FDA clearance to begin a Phase II clinical trial using the company's proprietary PLX-PAD cell product candidate intramuscularly for the treatment of Intermittent Claudication (IC), a subset of peripheral artery disease (PAD).

Published by Globes, Israel business news - http://www.globes-online.com - on May 9, 2012

Copyright of Globes Publisher Itonut (1983) Ltd. 2012

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Pluristem stem cells save girl's life

Public release date: 9-May-2012 [ | E-mail | Share ]

Contact: Dean Forbes dforbes@fhcrc.org 206-667-2896 Fred Hutchinson Cancer Research Center

SEATTLE For the first time, scientists at Fred Hutchinson Cancer Research Center have transplanted brain cancer patients' own gene-modified blood stem cells in order to protect their bone marrow against the toxic side effects of chemotherapy. Initial results of the ongoing, small clinical trial of three patients with glioblastoma showed that two patients survived longer than predicted if they had not been given the transplants, and a third patient remains alive with no disease progression almost three years after treatment.

"We found that patients were able to tolerate the chemotherapy better and without negative side effects after transplantation of the gene-modified stem cells than patients in previous studies who received the same type of chemotherapy without a transplant of gene-modified stem cells," said Hans-Peter Kiem, M.D., senior and corresponding author of the study published in the May 9 issue of Science Translational Medicine.

Kiem, a member of the Clinical Research Division at the Hutchinson Center, said that a major barrier to effective use of chemotherapy to treat cancers like glioblastoma has been the toxicity of chemotherapy drugs to other organs, primarily bone marrow. This results in decreased blood cell counts, increased susceptibility to infections and other side effects. Discontinuing or delaying treatment or reducing the chemotherapy dose is generally required, but that often results in less effective treatment.

In the current study, Kiem and colleagues focused on patients with glioblastoma, an invariably fatal cancer. Many of these patients have a gene called MGMT (O6-methylguanine-DNA-methyltransferase) that is turned on because the promoter for this gene is unmethylated. MGMT is a DNA repair enzyme that counteracts the toxic effect of some chemotherapy agents like temozolomide. Patients with such an unmethylated promoter status have a particularly poor prognosis.

A drug called benzylguanine can block the MGMT gene and make tumor cells sensitive to chemotherapy again, but when given with chemotherapy, the toxic effects of this combination are too much for bone marrow cells, which results in marrow suppression.

By giving bone marrow stem cells P140K, which is a modified version of MGMT, those cells are protected from the toxic effects of benzylguanine and chemotherapy, while the tumor cells are still sensitive to chemotherapy. "P140K can repair the damage caused by chemotherapy and is impervious to the effects of benzylguanine," Kiem said.

"This therapy is analogous to firing at both tumor cells and bone marrow cells, but giving the bone marrow cells protective shields while the tumor cells are unshielded," said Jennifer Adair, Ph.D., who shares first authorship of the study with Brian Beard, Ph.D., both members of Kiem's lab.

The three patients in this study survived an average of 22 months after receiving transplants of their own circulating blood stem cells. One, an Alaskan man, remains alive 34 months after treatment. Median survival for patients with this type of high-risk glioblastoma without a transplant is just over a year.

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Gene-modified stem cell transplant protects patients from toxic side effects of chemotherapy