ScienceDaily (Mar. 21, 2012) Powerful new cells created by Cardiff scientists from cheek lining tissue could offer the answer to disorders of the immune system. While the body's immune system protects against many diseases, it can also be harmful. Using white blood cells (lymphocytes), the system can attack insulin-producing cells, causing diabetes, or cause the body to reject transplanted organs.

A team from the School of Dentistry led by Professor Phil Stephens, with colleagues from Stockholm's Karolinska Institute, have found a new group of cells with a powerful ability to suppress the immune system's action.

The team took oral lining cells from the insides of patients' cheeks and cloned them. Laboratory tests showed that even small doses of the cells could completely inhibit the lymphocytes.

The breakthrough suggests that the cheek cells have wide-ranging potential for future therapies for immune system-related diseases. Existing immune system research has focused on adult stem cells, particularly those derived from bone marrow. The cheek tissue cells are much stronger in their action.

Dr Lindsay Davies, a member of the Cardiff team, said: "At this stage, these are only laboratory results. We have yet to recreate the effect outside the laboratory and any treatments will be many years away. However, these cells are extremely powerful and offer promise for combating a number of diseases. They are also easy to collect -- bone marrow stem cells require an invasive biopsy, whereas we just harvest a small biopsy from inside the mouth."

The findings have just been published online in Stem Cells and Development. The team has now been funded by the Medical Research Council to investigate the cloned cells further.

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The above story is reprinted from materials provided by Cardiff University.

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Powerful new cells cloned: Key to immune system disease could lie inside the cheek

The Stem Cell Transplant Program at the University of Virginia Health System recently performed the first two stem cell transplants in Virginia, using non-embryonic stem cells from umbilical cord blood.

The program offers both bone marrow and stem cell transplants, with a focus on cord blood, to treat leukemia, lymphoma, Hodgkins disease and other blood diseases.

While it will take several months to know how effective the cord blood transplants were, the initial results are promising, says Mary Laughlin, MD, an internationally known stem cell expert recruited to UVA to head the program. In both patients, the stem cells began engrafting producing new cells 14 days after the transplant instead of the 24 to 28 days it normally takes.

Why cord blood stem cells? As an obstetrician once told Laughlin: Something thrown away in my OB suite saves a life in your cancer suite.

The cord blood used for these stem cell transplants comes from placentas that otherwise would be discarded following childbirth, Laughlin says. The cord blood is used with the permission of the new parents, she says. By using cord blood stem cells instead of embryonic stem cells, UVAs program sidesteps the ethical, religious and political concerns commonly associated with stem cells, she says.

Other benefits: Cord blood stem cells are also faster and easier to collect than stem cells from other sources; they are also immune tolerant.

Speed is important because there is a narrow window of opportunity to perform a transplant when a patients disease is in remission. And because the cord blood stem cells are immune tolerant meaning they will not attack other cells in the body the chances of a successful transplant are higher and the donor match doesnt have to be as exact, giving more patients the opportunity to receive a transplant.

Stem cell transplants: Part of a fast-growing program Laughlin heads up a team of 29 staff members, including four additional transplant physicians, who began seeing patients in September. The demand for transplants has already been greater than Laughlin and her team expected. The program had initially planned to do 15 transplants in its first year. Instead, it expects to do 100.

Its reflective of this unmet need, Laughlin says. Patients who otherwise would have to travel many states away to have these same procedures, now they can do a fairly short drive from Roanoke, or down from Winchester. Because of our central location, its ideal for them.

What are stem cells? Learn more about how they work.

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First Stem Cell Transplants in Virginia Performed at UVA

Public release date: 20-Mar-2012 [ | E-mail | Share ]

Contact: Omar Montejo omontejo@miami.edu 305-243-5654 JAMA and Archives Journals

CHICAGO Among patients with end-stage renal disease undergoing living-related kidney transplants, the use of bone-marrow derived mesenchymal (cells that can differentiate into a variety of cell types) stem cells instead of antibody induction therapy resulted in a lower incidence of acute rejection, decreased risk of opportunistic infection, and better estimated kidney function at 1 year, according to a study in the March 21 issue of JAMA.

Induction therapy, routinely implemented in organ transplant procedures, consists of use of biologic agents to block early immune activation. New induction immunosuppressive protocols with increased efficacy and minimal adverse effects are desirable. "Antibody-based induction therapy plus calcineurin inhibitors (CNIs) reduce acute rejection rates in kidney recipients; however, opportunistic infections and toxic CNI effects remain challenging. Reportedly, mesenchymal stem cells (MSCs) have successfully treated graft-vs.-host disease," according to background information in the article.

Jianming Tan, M.D., Ph.D., of Xiamen University, Fuzhou, China and colleagues examined the effect of autologous (derived from the same individual) MSC infusion as an alternative to anti-IL-2 receptor antibody for induction therapy in adults undergoing living-related donor kidney transplants. The randomized study included 159 patients. Patients were inoculated with marrow-derived autologous MSC at kidney reperfusion and two weeks later. Fifty-three patients received standard-dose and 52 patients received low-dose CNIs (80 percent of standard); 51 patients in the control group received anti-IL-2 receptor antibody plus standard-dose CNIs.

Patient and graft survival at 13 to 30 months was similar in all groups. The researchers found that after 6 months, 4 of 53 patients (7.5 percent) in the autologous MSC plus standard-dose CNI group and 4 of 52 patients (7.7 percent) in the low-dose group compared with 11 of 51 controls (21.6 percent) had biopsy-confirmed acute rejection. Renal function recovered faster among both MSC groups showing increased estimated glomerular filtration rate (eGFR; a measure of kidney function) levels during the first month after surgery than the control group.

The authors also found that during the 1-year follow-up, combined analysis of MSC-treated groups revealed significantly decreased risk of opportunistic infections than the control group.

"In our prospective randomized trial on a large patient population, autologous MSCs could replace anti-IL-2 receptor-induction therapy in living-related donor kidney transplants. Recipients of autologous MSCs showed lower frequency of biopsy-confirmed acute rejection in the first 6 months than the control group," the researchers write.

"Extended monitoring of study participants will allow assessment of the long-term effects of autologous MSCs on renal allograft function, survival, and safety."

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Use of stem cells for adults receiving related donor kidney transplants appears to improve outcomes

By Ron Winslow

Doctors at Yale University have successfully implanted a biodegradablescaffold seeded with a four-year-old girls own bone-marrowcells to help treat a serious heart defect, as WSJs Heartbeat column describes.

The tube about three inches long is made of polyester material similar to that used in the manufacture of dissolvable sutures. Six months after Angela Irizarrys surgery, it had disappeared, replaced by a bioengineered conduit that acts like a normal blood vessel.

The vanishing act for the scaffold was expected, but what happens to the cells, including stem cells, that spawned the new vessel?

Much to the researchers surprise, says Chris Breuer, the Yale pediatric surgeon leading the experimental tissue-engineering project, the cells go away too.

Stem cells and certain other bone-marrow cells have building-block properties that make them the foundation for more specialized cells that grow into the bodys various tissues and structures. Researchers have long believed that stem cells transplanted into heart tissue, for instance, would be a primary component of whatever new tissue that grew as a result.

A lot of people think that when you put cells in, they turn into whatever cells you want them to turn into, Breuer tells the Health Blog. Weve clearly shown that doesnt happen in our graft.

Indeed, in experiments performed to learn how the tubes morphed into blood vessels, Breuer and his colleagues transplanted their scaffold seeded with human cells into mice bred with deficient immune systems to prevent rejection of the cells. Within a few days, the human cellswere gone, replaced within the scaffold by mouse cells, including cells characteristic of those that line the inner wall of blood vessels.

Initially, I refused to believe it, Breuer says. I redid the experiment three different ways and saw the same thing every time.

The upshot: Transplanted cells that have a quality of stem cells dont buildnew parts themselves, he says.They cause the body to induce regeneration.

Continue reading here:
In Treatment of Child’s Heart Defect, Doctors Find a Stem-Cell Surprise

Public release date: 21-Mar-2012 [ | E-mail | Share ]

Contact: Stephen Rouse RouseS@cardiff.ac.uk 44-292-087-5596 Cardiff University

Powerful new cells created by Cardiff University scientists from cheek lining tissue could offer the answer to disorders of the immune system.

While the body's immune system protects against many diseases, it can also be harmful. Using white blood cells (lymphocytes), the system can attack insulin-producing cells, causing diabetes, or cause the body to reject transplanted organs.

A team from Cardiff's School of Dentistry led by Professor Phil Stephens, with colleagues from Stockholm's Karolinska Institute, have found a new group of cells with a powerful ability to suppress the immune system's action.

The team took oral lining cells from the insides of patients' cheeks and cloned them. Laboratory tests showed that even small doses of the cells could completely inhibit the lymphocytes.

The breakthrough suggests that the cheek cells have wide-ranging potential for future therapies for immune system-related diseases. Existing immune system research has focussed on adult stem cells, particularly those derived from bone marrow. The cheek tissue cells are much stronger in their action.

Dr Lindsay Davies, a member of the Cardiff team, said: "At this stage, these are only laboratory results. We have yet to recreate the effect outside the laboratory and any treatments will be many years away. However, these cells are extremely powerful and offer promise for combating a number of diseases. They are also easy to collect bone marrow stem cells require an invasive biopsy, whereas we just harvest a small biopsy from inside the mouth."

The findings have just been published online in Stem Cells and Development. The team has now been funded by the Medical Research Council to investigate the cloned cells further.

###

Read more:
Key to immune system disease could lie inside the cheek

Nigeria launches its first ever bone marrow registry, which should make it easier to find matches for black people around the world.

By Jef Akst | March 19, 2012

Bone marrow transplants, or hematopoietic stem cell transplantations (HSCT), treat more than 70 different diseases, including some types of leukemia, lymphoma, and sickle cell anaemia. But such treatment often requires the matching of strangers for their human leukocyte antigen (HLA) tissue type. And while 70 percent of Caucasian patients are successfully matched, only 17 percent of black people in the United States are as lucky, according to The New York Stem Cell Foundation, likely because only 8 percent of donors in US registries are black.

The Bone Marrow Registry in Nigeria (BMRN), the countrys first ever bone marrow registry and the continents second (South Africa having the only other accredited registry), aims to change all that. The registry follows the excitement surrounding Nigerias first bone marrow transplant last October, in which a young sickle cell anaemia patient received bone marrow from a sibling. In addition to providing an invaluable service to the people of Nigeria, the registry, launched by Seun Adebiyi of Yale University, should help black patients around the world find matched donors. The launch of the registry was discussed at the NCD Child Conference currently being held in San Francisco.

Adebiyi also plans to establish another Nigerian source for stem cell transplantsan umbilical cord blood bank. With as little as $75,000, we could build [a cord blood bank] in Nigeria by the end of this year instead of discarding this valuable source of stem cells, he said in a Lancet press release. There are almost 400 distinct ethnic groups and over 154 million people in Nigeria alone, and there is a huge population of umbilical stem cells just waiting to be banked in the maternity wards of hospitals around the country.

By Cristina Luiggi

An Italian university is investigating whether a professor was right to teach a course denying a causal link between HIV and AIDS.

By Hannah Waters

Replacing immune cells in a mouse model of Rett syndrome, a developmental brain disorder, improved symptoms, suggesting a new target for treatment.

By Megan Scudellari

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New African Bone Marrow Registry

For about three days in January, Matt Ladd said he didnt know whether it was day or night, what was top or bottom.

I was probably as sick as Ive ever been, said Ladd, a Billings game warden, in a telephone interview from Seattle. As things got progressively worse and worse, I was really concerned about what was going on right then.

Ladd was headed to Seattle for stem cell bone marrow transplant surgery when an infection he was being treated for worsened. The infection started around a catheter inserted into his chest to deliver chemotherapy drugs. The chemo was battling Ladds acute myeloid leukemia and myelodysplastic syndrome, which was diagnosed in September. His bone marrow wasnt producing enough red blood cells.

The chemo worked. He was in remission and on his way to Seattle for a bone marrow transplant when the infection sent him into a rapid downward spiral. Because of the location of the catheter, the infection attacked his heart valves. During the struggle with the infection, his kidneys failed, his body retained water and he swelled up.

The infection scuttled plans for the bone marrow transplant surgery. With his kidneys failing, he had to undergo dialysis. As a final insult to his immune system, he had to take more chemotherapy since the surgery had been delayed and doctors feared the MDS might return.

My body and kidneys didnt respond well to the chemo, he said.

More than a month after he was scheduled to undergo surgery, Ladd is living in an apartment north of Seattle as family members rotate caretaking duties. His wife, Maureen, a math teacher at Billings West High, is holding down the fort at home, trying to maintain a sense of normalcy for their sons, Dylan, Logan and Jack.

What was going to be a short process has become a very long process, Maureen said.

Now the Ladds are waiting to hear whether Matt and his sister, Jessica Cook, will take part in a Seattle Cancer Center Alliance study of a new method of bone marrow transplantation. Since Ladds kidneys have been injured, he would normally have to have a reduced-intensity transplant used for the elderly and those with health issues, Maureen explained.

The experimental method would treat Cook, Ladds only sibling and a bone marrow transplant match, with Lipitor prior to the surgery. The cholesterol-lowering drug has shown promise in preventing reactions to transplants. If they are accepted for the study, it would mean a further delay of surgery, since Cook would have to be on the drug for a couple of weeks prior to the operation.

Read more from the original source:
Billings game warden fights cancer complications

The same species that submitted itself to experimentation for treatments to human cancers is now getting a cure with N.C. State's first canine bone marrow transplant.

In 2008, Dr. Steven Suter, assistant professor of oncology, began performing bone marrow transplants, BMT, on dogs. N.C. State is the only university in the world that offers this treatment. While private practices do exist, mainly on the west coast, they have treated few dogs. People have traveled from across the country to utilize these services.

Once I became an oncologist, I realized that this could probably be done now in a clinical setting if the appropriate machines could be found, apheresis machines. Once I got a hold of some of these machines, I started collecting peripheral blood progenitor cells from a few research colony dogs. After I showed we could do that, we moved on to start transplanting client-owned dogs. We opened our canine BMT unit in October 2008, Suter said.

Until recently, the transplants used stem cells from the dogs' own blood, so only those who had a disease in remission could be treated. The treatment was typically used on dogs with lymphoma.

The cure rate of dogs with lymphoma treated with chemotherapy is less than 5 percent, so I felt we could do better on that front with BMT, Suter said. We have modified the protocol extensively since the first 24 dogs, so we are hoping it will now be better.

However this all changed with two Cavalier King Charles Spaniels, Chip and Zeke, earlier this year. Zeke was diagnosed with acute lymphocytic leukemia in December 2011. This disease could only be treated by use of donor bone marrow. Chip, a littermate, was the prime choice.

We do require a donor, since we can not harvest progenitor cells from the patient. Leukemia patients have too many cancer cells floating around in their blood, so the machine would harvest them also. So, we find a matched donor who does not have cancer obviously, and harvest the cells from them, Suter said. We don't use this procedure regularly to treat dogs with leukemia ... we've treated two dogs with leukemia. We use it mainly to treat dogs with lymphoma, which is a very different disease."

The owners of the dogs met for the first time at N.C. State for the procedure to take place.

Jason Hefner, a fourth year in veterinary medicine, worked with Zeke while he was here.

To our knowledge, only one previous case has been treated with a donor. Zeke had a great disposition, and I looked forward to visiting him each morning for his treatments. Zeke is now in New York and looking forward to a happy and healthy life, Hefner said.

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University gives dog a bone marrow transplant

Edited by M. A. Hayat 384 pp, $209 New York, NY, Springer, 2012 ISBN-13: 978-9-4007-2015-2

Stem cells and cancer stem cells are 2 distinct, evolving, and promising areas of research. Hematopoietic stem cells are already used in the treatment of bone marrow failure and hematologic malignancies, and there is now great interest in isolating stem cells from other organs for use in replenishing damaged tissue in the heart, brain, bones, and other organs and structures. In contrast, cancer stem cells, a newly recognized component of some cancers, have some properties of pluripotent stem cells in that they replicate without normal cell cycle regulation and apoptosis. Moreover, they are naturally resistant to chemotherapy because of drug-exuding pumps, DNA repair proteins, and dormancy; thus, these cells are now suspected to be the root cause of relapse and metastasis after conventional therapies in some malignancies, especially leukemia. Targeting cancer stem cells in addition to cancer cells may therefore lead to better eradication of cancer than is presently possible.

Read more from the original source:
Stem Cells and Cancer Stem Cells: Therapeutic Applications in Disease and Injury, Volume 2 [Book and Media Reviews]

14 March 2012 Last updated at 09:00 ET By Jane O'Brien BBC News, Maine

Please turn on JavaScript. Media requires JavaScript to play.

One of Doreen Flynn's daughters, 13-year-old Jordan, says the whole transplant process scares her

A mother in the US is desperate to find bone marrow donors to save the lives of her three daughters who are critically ill from a rare blood disorder. Now, she is challenging a federal law barring her from compensating prospective donors.

Thousands of Americans who need transplants die every year because they cannot find a suitable donor, advocates say.

They propose a controversial way to encourage more people to come forward: Pay them.

"It is widening the donor pool. A lot of times employers don't pay for the time off that these donors take from work," says Doreen Flynn of Lewiston, Maine.

"So I think in those instances those people can say, 'you know I can do that,' knowing that there will be a support system for them at the end."

Ms Flynn's three daughters have a rare genetic blood disorder called Fanconi Anaemia. Their bone marrow does not make enough blood cells to keep them healthy and their only hope for survival is a transplant.

It is against US law to sell body parts - including bone marrow. But last year, Ms Flynn won a court ruling in favour of compensating donors whose blood stem cells are collected using a process called aphaeresis.

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Should it be legal to pay for bone marrow donations?

Public release date: 12-Mar-2012 [ | E-mail | Share ]

Contact: Sarah Jackson sarah.jackson@the-jci.org 919-684-0620 Journal of Clinical Investigation

The liver is unique among mammalian organs in its ability to regenerate after significant tissue damage or even partial surgical removal. Laurie DeLeve and her colleagues at the University of Southern California in Los Angeles wanted to better understand which cells are specifically responsible for driving liver regeneration. A specialized cell type, known as liver sinusoidal endothelial cells, has generally been thought to promote regeneration of liver tissue. However, the DeLeve team suspected that stem cells and progenitor cells, which have the capacity to differentiate into mature cell types, might be responsible for stimulating liver regeneration by generating hepatocyte growth factor. Using a rat model system, they first identified the presence of stem and progenitor cells that give rise to liver sinusoidal endothelial cells in both the liver and the bone marrow. They next sought to determine which population of stem and progenitor cells are required for regeneration. DeLeve and colleagues found that the bone marrow-derived cells were not required for liver cell proliferation in the absence of damage. In contrast, following surgical removal of a portion of the rat liver, an infusion of bone marrow-derived progenitor cells was required for liver regeneration. These results improve our understanding of how liver tissue can regenerate following damage and may shed light on liver complications in patients with suppressed bone marrow tissue.

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TITLE: Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats

AUTHOR CONTACT: Laurie D. DeLeve University of Southern California Keck School of Medicine, Los Angeles, CA, USA Phone: 323-442-3248; Fax: 323-442-3238; E-mail: deleve@usc.edu View this article at: http://www.jci.org/articles/view/58789?key=21e2857b21106f232595

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

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Restoring what's lost: Uncovering how liver tissue regenerates

Public release date: 12-Mar-2012 [ | E-mail | Share ]

Contact: Sarah Jackson press_releases@the-jci.org 919-684-0620 Journal of Clinical Investigation

EDITOR'S PICK Restoring what's lost: uncovering how liver tissue regenerates

The liver is unique among mammalian organs in its ability to regenerate after significant tissue damage or even partial surgical removal. Laurie DeLeve and her colleagues at the University of Southern California in Los Angeles wanted to better understand which cells are specifically responsible for driving liver regeneration. A specialized cell type, known as liver sinusoidal endothelial cells, has generally been thought to promote regeneration of liver tissue. However, the DeLeve team suspected that stem cells and progenitor cells, which have the capacity to differentiate into mature cell types, might be responsible for stimulating liver regeneration by generating hepatocyte growth factor. Using a rat model system, they first identified the presence of stem and progenitor cells that give rise to liver sinusoidal endothelial cells in both the liver and the bone marrow. They next sought to determine which population of stem and progenitor cells are required for regeneration. DeLeve and colleagues found that the bone marrow-derived cells were not required for liver cell proliferation in the absence of damage. In contrast, following surgical removal of a portion of the rat liver, an infusion of bone marrow-derived progenitor cells was required for liver regeneration. These results improve our understanding of how liver tissue can regenerate following damage and may shed light on liver complications in patients with suppressed bone marrow tissue.

TITLE: Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats

AUTHOR CONTACT: Laurie D. DeLeve University of Southern California Keck School of Medicine, Los Angeles, CA, USA Phone: 323-442-3248; Fax: 323-442-3238; E-mail: deleve@usc.edu

View this article at: http://www.jci.org/articles/view/58789?key=21e2857b21106f232595

ONCOLOGY New Determinant of Human Breast Cancer Metastasis Discovered

Researchers at the University of Kentucky's Markey Cancer Center in Lexington, KY have provided new insight as to why the most severe subtype of breast cancer in humans frequently metastasizes. Tumor cells can exploit a cellular program that promotes cell migration and reduces adhesion between cells to spread to distant sites in the body (metastasis). This cellular program, known as the epithelial-mesenchymal transition, is normally restricted to wound healing, tissue remodeling and embryonic development. Increasing cell motility requires a decrease in E-cadherin, which functions to promote cell-cell adhesion. Led by Binhua Zhou, the research team identified G9a as a major repressor of E-cadherin expression. They found that G9a interacts with Snail, which can repress gene expression, to modify the E-cadherin promoter and block expression of the E-cadherin gene. Their findings establish that G9a is an important determinant of metastasis in the most severe sub-type of breast cancer, and suggest the development of new therapeutics targeting this pathway could potentially disrupt the metastatic disease.

TITLE: G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer

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JCI early table of contents for March 12, 2012

Cancer sufferer Pamela Bou Sejean wants your help to save her life

Pamela Bou Sejean has Hodgkin's Lymphoma and needs a stem cell transplant. Picture: Alison Wynd Source: News Limited

PAMELA Bou Sejean is fighting for her life.

After 16 months battling an aggressive form of Hodgkin's Lymphoma, the 26-year-old has turned to Facebook in a last ditch bid to find the stem cell donor to keep her alive.

TheVictorian woman in Belmont does not match with any registered bone marrow donor in the world so is now pleading for the public to come forward to be blood tested for a possible match.

"I don't know how much time I have, I get too afraid to ask," Ms Bou Sejean told the Geelong Advertiser.

"I want to focus on what we're doing now.

"The waiting process is hard."

With her life in the balance, Ms Bou Sejean's brother Matt a week ago set up the Facebook page How You Can Help Cure Pamela.

There, Facebook users are told about her fight and how to be blood tested for a possible stem cell match.

Visit link:
Stem cells are my last hope. Can you help?

Pamela Bousejean has Hodgkin's Lymphoma and needs a stem cell transplant. Picture: Alison Wynd Source: News Limited

PAMELA Bou Sejean is fighting for her life.

After 16 months battling an aggressive form of Hodgkin's Lymphoma, the 26-year-old has turned to Facebook in a last ditch bid to find the stem cell donor to keep her alive.

TheVictorian woman in Belmont does not match with any registered bone marrow donor in the world so is now pleading for the public to come forward to be blood tested for a possible match.

"I don't know how much time I have, I get too afraid to ask," Ms Bou Sejean told the Geelong Advertiser.

"I want to focus on what we're doing now.

"The waiting process is hard."

With her life in the balance, Ms Bou Sejean's brother Matt a week ago set up the Facebook page How You Can Help Cure Pamela.

There, Facebook users are told about her fight and how to be blood tested for a possible stem cell match.

Mr Bou Sejean who, like the rest of the family, does not match with his sister said "the cure for Pamela is in the body of hundreds of people out there."

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BE THE CHANGE: Stem cells are Pamela's last hope - can you help?

by Maggie Ruper

WHAS11.com

Posted on March 7, 2012 at 11:50 PM

Updated yesterday at 12:01 AM

LOUISVILLE, Ky. (WHAS11) -- New research published Wed. in the journal Science Translation Medicine, shows organ transplant recipients may not require anti-rejection medication after surgery.

The study, authored by University of Louisville professor Suzanne Ildstad, M.D., suggests bone marrow stem cells are able to trick the recipients immune system into thinking the donated organ is part of the patients natural self. It therefore eliminates the need for patients to take dozens of daily anti-rejection drugs.

Normally, if I have to transplant a kidney into a patient they have to take immunosuppression drugs for their lifetime and that's about 15 to 25 pills a day, said Ildstad.

Louisville native and father of four, Rob Waddell underwent the procedure in 2009 at Northwestern Memorial Hospital. He suffered from Polycystic Kidney Disease since he was 11 years old. His new kidney and the stem cells were donated to him by his next door neighbor.

It was a match and the rest is history. He's what I call my guardian angel," said Wadell.

The results were considered important because the technique worked for patients who did not have well-matched or related donors.

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UofL Professor’s study: Stem cells eliminate need for anti-rejection drugs

WASHINGTON (AP) -- An experimental technique seems to be freeing some kidney transplant patients from having to take anti-rejection drugs.

Researchers transplanted certain cells from the kidney donor's bone marrow along with the new organ. Five of eight transplant recipients who tried the method so far were off immune-suppressing medication up to 2 years later, the researchers reported Wednesday.

The preliminary results were considered important enough to be published in the journal Science Translational Medicine even though the study still is under way, because the technique worked for patients who didn't have well-matched or related donors.

The idea is that if a sort of twin immune system takes root and lasts, it can allow the patient's body to accept the foreign organ and not attack it, said study co-author Dr. Suzanne Ildstad of the University of Lousville. Scientists call it chimerism.

"The most reliable indicator of really being successful at taking someone off immune-suppressing drugs is durable chimerism," says Ildstad, who teamed with doctors at Chicago's Northwestern Memorial Hospital for the research.

Transplant recipients usually must take multiple immune-suppressing pills for life to prevent rejection of their new organ. Those drugs cause lots of side effects, such as raising the risk of cancer and kidney damage.

Other scientists are attempting to tap bone marrow to induce immune tolerance, with varying success.

Ildstad's approach transfuses a special mix of bone marrow cells including blood-producing stem cells and another type named "facilitating cells" that are thought vital for a successful transplant. She filters out still other cells that can become too aggressive and cause a life-threatening disorder named graft-versus-host disease.

Transplant recipients had radiation and chemotherapy, not destroying their own bone marrow but tamping it down to make space for the donated cells, explained study co-author Dr. Joseph Leventhal, a Northwestern transplant surgeon. Five patients who had the dual immunity a year later were weaned off all drugs. Two others whose hybrid immunity faded are faring well using a low dose of one anti-rejection drug. One patient needed a repeat transplant after an infection and didn't get to try weaning.

Much more study is needed to find the best approach but "the results are striking," Dr. Tatsuo Kawai of Massachusetts General Hospital wrote in an accompanying editorial. He is part of a team that in 2008 reported the only other success with a small number of mismatched transplants.

See original here:
Cells may spare kidney transplant rejection drugs

Approach Could Free Organ Patients From Anti-Rejection Drugs

March 7, 2012 -- New research holds the promise of freeing many organ transplant patients from a lifetime of anti-rejection drugs.

In the first study of its kind, eight kidney transplant patients received stem cells from their kidney donors manipulated to trick their bodies into accepting the foreign organ as its own.

Transplant recipients who are not perfectly matched with their donors typically take several drugs a day for the rest of their lives to keep their bodies from rejecting the new organ and to treat the side effects of those drugs.

Lindsay Porter, who was the last of the eight patients enrolled in the new study, had her kidney transplant in the summer of 2010 and was weaned off all anti-rejection drugs within a year.

The Chicago actress and mother says she feels better than she has in 15 years and sometimes has to remind herself that she had a kidney transplant.

I was 45 when I had the surgery, and I knew I would probably need another kidney at some point, she tells WebMD. The opportunity to have a transplant that would last for the rest of my life and to avoid all of those drugs was very appealing.

The ongoing research is the culmination of many years of work by researcher Suzanne Ildstad, MD, of the University of Louisville, and other researchers, including transplant surgeon Joseph Leventhal, MD, PhD, of Chicagos Northwestern University.

The new wrinkle is that organ donors who are not a perfect genetic match with the patient donate blood as well as a kidney for the procedure.

Bone marrow stem cells collected from the blood were processed in an 18-hour procedure to remove cells associated with organ rejection, leaving behind facilitating cells that do not promote rejection, Ildstad says.

Originally posted here:
Altered Stem Cells Limit Transplant Rejection

Donating a kidney may save a person's life - but only if the conditions are precise.

Kidney donors must be related and immunologically matched to their donors and even then, the recipient must take a lifetime of anti-rejection medications, which dont guarantee the organ won't be rejected.

But a new clinical trial from Northwestern Memorial Hospital in Chicago, Ill. has shown how stem cells can be used to trick a recipients immune system into believing the new organ has been part of that persons body all along.

The breakthrough has the potential to eliminate both the risks associated with kidney transplantation and the need for anti-rejection medications within one year after surgery.

Its the holy grail of transplantation, said lead author Dr. Joseph Leventhal, transplant surgeon at Northwestern Memorial Hospital and associate professor of surgery and director of kidney and pancreas transplantation at Northwestern University Feinberg School of Medicine in Chicago, Ill. This notion of being able to achieve tolerance through donor derived cells has been around for more than 50 years, but its translation to the clinic has been quite elusive. This article details the first successful attempt of this in mismatched and unrelated kidney recipients.

The research was published Wednesday in the journal Science Translational Medicine, and it is the first study of its kind in which the donor and recipient were not related and did not have to be immunologically matched. Only 25 percent of siblings are immunologically identical, severely limiting the possibility of being a kidney donor.

The procedure worked by extracting a little bit more from the kidney donor than just their kidney. They also donated part of their immune system. About one month before surgery, bone marrow stem cells were collected from the donor and then enriched with facilitating cells becoming stem cells that will ultimately fool the donors immune system allowing the transplant to succeed.

One day after the kidney transplant occurs, the facilitating cell-enriched stem cells are also transplanted in the recipient, which then prompts the formation of stem cells in the bone marrow. This then causes specialized immune cells similar to the donors immune cells to develop, creating a dual bone marrow system environment, so both the donors immune system and the recipients immune system function inside the persons body.

Leventhal said that the ultimate goal is for the recipient to initially take anti-rejection medications but then slowly wean off of them within a year. According to Leventhal, the drugs come with their own share of negative side effects.

The foundation of clinical transplantation revolves around the use of medicines and suppressive drugs to control the immune system, Leventhal said. These drugs have been very successful in reducing the rates of loss of organs due to acute rejection where side effects include increase risk of infection and cancer, and metabolic side effects, such as the increase risk of hypertension and bone disease. But the drugs themselves are potentially harmful to the organs we transplant. Despite our ability to reduce rates of acute rejection, most individuals go on to lose organs because of chronic (long-term) rejection.

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Stem cell research allows for mismatched kidney transplants

(AP) An experimental technique seems to be freeing some kidney transplant patients from having to take anti-rejection drugs.

Researchers transplanted certain cells from the kidney donor's bone marrow along with the new organ. Five of eight transplant recipients who tried the method so far were off immune-suppressing medication up to 2 1/2 years later, the researchers reported Wednesday.

The preliminary results were considered important enough to be published in the journal Science Translational Medicine even though the study still is under way, because the technique worked for patients who didn't have well-matched or related donors.

The idea is that if a sort of twin immune system takes root and lasts, it can allow the patient's body to accept the foreign organ and not attack it, said study co-author Dr. Suzanne Ildstad of the University of Lousville. Scientists call it chimerism.

"The most reliable indicator of really being successful at taking someone off immune-suppressing drugs is durable chimerism," says Ildstad, who teamed with doctors at Chicago's Northwestern Memorial Hospital for the research.

Transplant recipients usually must take multiple immune-suppressing pills for life to prevent rejection of their new organ. Those drugs cause lots of side effects, such as raising the risk of cancer and kidney damage.

Other scientists are attempting to tap bone marrow to induce immune tolerance, with varying success.

Ildstad's approach transfuses a special mix of bone marrow cells including blood-producing stem cells and another type named "facilitating cells" that are thought vital for a successful transplant. She filters out still other cells that can become too aggressive and cause a life-threatening disorder named graft-versus-host disease.

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Transplant recipients had radiation and chemotherapy, not destroying their own bone marrow but tamping it down to make space for the donated cells, explained study co-author Dr. Joseph Leventhal, a Northwestern transplant surgeon. Five patients who had the dual immunity a year later were weaned off all drugs. Two others whose hybrid immunity faded are faring well using a low dose of one anti-rejection drug. One patient needed a repeat transplant after an infection and didn't get to try weaning.

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New treatment for kidney transplant patients may reduce need for anti-rejection drugs

Kidney transplant-recipients have to take immunosuppressant drugs for the rest of their lives to prevent rejection.

A. MASSEE/SCIENCE PHOTO LIBRARY

Graft-versus-host disease (GvHD) is a common and often deadly complication of bone-marrow transplantation that occurs when immune cells from an unrelated donor attack the transplant recipients tissue. Now, researchers have for the first time managed to completely replace peoples bone-marrow-derived stem cells with those from unrelated donors without causing GvHD1. And because of this, the recipients could also accept kidneys from the same donors without the need for drugs that suppress the immune system.

The outcome has been amazing, says Lindsay Porter, a 47-year-old Chicago resident with polycystic kidney disease who was one of the study subjects. She has been off immunosuppressive drugs for seven months. I feel so normal, it feels like its not a big deal.

But according to experts in the field, the findings, published today in Science Translational Medicine1, are a huge deal. Its kind of difficult to believe, says Tatsuo Kawai, a transplant surgeon at Massachusetts General Hospital in Boston, who wrote a commentary to accompany the paper. Its almost common sense to have GvHD in mismatched individuals.

The latest study builds off of work Kawai and his colleagues began fourteen years ago, when they launched the first clinical trial that attempted to use bone marrow to induce immune tolerance for kidney recipients, to avoid the sometimes dangerous side effects of life-long immosuppressive therapy.

Working first in people with perfectly immune-matched siblings2 and then with partially mismatched donor-recipient pairs3, the researchers showed that the majority of individuals could achieve stable kidney function and successfully wean off of their immunosuppressants with few problems in one case for up to nine years. But the study subjects only maintained noticeable levels of the foreign bone marrow for a few weeks, and the protocol didnt work for everybody. Some researchers speculated that maintaining higher levels of donor immune cells for longer could help to improve the success rate.

For the latest study, a team led by Suzanne Ildstad, director of the University of Louisvilles Institute for Cellular Therapeutics in Kentucky, found a way to avoid GvHD by using a regimen involving chemotherapy, radiation and blood stem cells manipulated to eliminate those that cause GvHD while retaining specialized bone-marrow-derived cells they called facilitating cells.

Ildstad and her colleagues report that five of eight people who underwent the treatment were able to stop all immunosuppressive therapy within a year after their kidney and stem-cell transplants, four of which came from unrelated donors. Notably, all of these patients maintained entirely donor-derived immune systems with no signs of GvHD. Ildstad and her team have since treated seven more people. We continue to see good results, she says.

It might be premature, however, to say for certain that the trial participants are in the clear. The question is: will these patients remain free of GvHD? says David Sachs, director of the Transplantation Biology Research Center at Massachusetts General Hospital. You would hope that its true, but its a little early to claim that.

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Drug-free organ transplants without tissue matching