Stem Cell Clinic

Stem cell treatments reaching patients

By Stem Cell Treatment

Neurosurgeon and stem cell researcher, Joseph Ciacci M.D. will soon start a clinical trial of stem cells to treat paralysis from spinal cord injury.

After many years of waiting, a flood of new regenerative-cell therapies is finally reaching patients. Hundreds of clinical trials for these experimental treatments are under way across the world.

In the United States, 774 trials with stem or other regenerative cells are open to patients or soon will be, according to clinicaltrials.gov, which lists government-approved clinical testing in this country and abroad. Of that total, 147 are taking place in California.

One of the most difficult tests involving stem cells repairing spinal-cord damage that has caused complete loss of movement and sensation below the injury site is set to begin soon at UC San Diego.

Patients in that study will get injections of fetal-derived neural stem cells in and around the injury site, along with physical therapy and immune-system drugs in case theres a reaction to the stem cells. The trial will use a device that delivers precisely targeted micro-injections of cells to the targeted areas.

The clinical trial will test safety and look for early signs of efficacy, said Dr. Joseph Ciacci, a UC San Diego neurosurgeon leading the testing.

A study published a year ago found that in rats with spinal-cord injuries, the neural stem cells significantly improved movement in the hind paws. Ciacci, who co-authored that study, saw the cells proliferate and fill in a spinal-cord cavity that had resulted from the injuries. Such results supported testing the therapy in people, he said, but he declined to say whether he expected to see any improvement in those patients.

I really dont know, because its not been done, Ciacci said.

The clinical trial is expected to start in June. Its intended for adults 18 to 65 years old who suffered their injury at least one year ago but no more than two years ago. For more information, visit utsandiego.com/ucsdspinal or call Amber Faulise at (858) 657-5175.

Another type of stem cells, mesenchymal stromal, might be described as the duct tape of regenerative cells. Generally derived from bone marrow, they are being tested for treatment of pulmonary fibrosis, multiple sclerosis, kidney transplants, liver cirrhosis, osteoarthritis of the knee, stroke and many other conditions. Worldwide, 226 trials are being conducted with these cells, including 45 in the U.S. and 12 in California, according to clinicaltrials.gov.

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Stem cell treatments reaching patients

Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory …

By Stem Cell Treatment

We did this randomised, open-label, phase 2 study at seven German transplantation centres. We enrolled patients with aggressive B-cell or T-cell lymphoma and primary refractory disease, early relapse (2), busulfan (12 mg/kg oral or 96 mg/kg intravenous), and cyclophosphamide (120 mg/kg) was followed by allogeneic stem-cell transplantation. Patients were randomly assigned (1:1) to receive rituximab (375 mg/m2 on days 21, 28, 35, 42, 175, 182, 189, and 196) or not. Allocation was done with a centralised computer-generated procedure; patients were stratified by histological subtype (B-cell vs T-cell lymphoma) and donor match (HLA-identical vs non-identical). Neither investigators nor patients were masked to allocation. The primary endpoints were the incidence of acute graft-versus-host disease grade 24 in each treatment group and overall survival at 1 year in both groups combined. All analyses were done for the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00785330.

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#Shake4Mike: 'I wanted to be his rock in return'

By Stem Cell Doctors

He was still waiting to hear back from a job interview, so I assumed it was about that and I got really excited, she says. I tried to ring a few times, and eventually I got through over quite a patchy line. He said, 'I think Ive got leukaemia. When you hear those words, you know how serious it is. I just told him, 'Im going to get home as quickly as I can.

The news that followed was devastating. Mike, 29, was diagnosed with acute lymphoblastic leukaemia and is currently undergoing intense chemotherapy six times a week at Bristol Royal Infirmary. Such is the severity of his condition that doctors have said he needs a stem-cell transplant to save his life and time is running out.

As has been widely reported this week, his family, who live in Somerset, have only until the start of July, when his chemotherapy course ends, to find a suitable donor. Normally a third of people requiring the operation are able to find a sibling match. All of his three brothers have already been tested, but none has been successful.

He and his loved ones are now searching the Anthony Nolan stemcell donor register for a match with a stranger willing to help. The charity warns, however, that it can normally find a suitable donor for only around half the people who need a life-saving stem-cell transplant.

Kate, as a result, has taken matters into her own hands. This week, she launched a public campaign for people to sign up to the register, urging social media users to post silly videos of themselves shaking their faces from side to side something the couple used to film each other doing to promote the campaign she has called #Shake4Mike.

Her hope, of course, is that more signatories to the register will boost her fiancs chances of finding a donor and she has been inundated with responses. Some have been so funny theyve made me laugh out loud.

Indeed, in conversation, the Nottingham University graduate is strikingly upbeat and resilient. But optimism in the face of tragedy is a skill she has already been forced to master. In 2005, her 59-year-old father, David, died suddenly at the family home in Aylesbury, Buckinghamshire, after developing a blood clot following an operation on a hip he had broken skiing. He had just eaten his Sunday roast and walked on his crutches to the living room and died.

A few weeks later, her grandparents followed him. In 2008 her mother, Ali, invited her best friend, Simon Blackett, to move in to help support the family. Within two months, the 38-year-old suffered a fatal brain haemorrhage.

It was a year after this latest loss that the couple first met. Kate says her fianc has helped turn her life around and that, ever since she received that phone call in Burma, she has been determined to be his rock in return.

Still, the journey home was in itself enough to test her emotional strength. She remembers a horrendous 48-hour blur of buses and planes. Mum picked me up straight from Heathrow and drove me to the hospital. I thought when I saw her Id break down, but shes really strong and that helped so much. When I got to the hospital and saw him he looked pale, but other than that it was just a relief to be with him, says Kate.

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#Shake4Mike: 'I wanted to be his rock in return'

Epigenetic mechanisms distinguishing stem cell function, blood cancer decoded

By Stem Cell Medicine

Researchers at Dartmouth's Norris Cotton Cancer Center have published results from a study in Cell Reports that discovers a new mechanism that distinguishes normal blood stem cells from blood cancers.

"These findings constitute a significant advance toward the goal of killing leukemia cells without harming the body's normal blood stem cells which are often damaged by chemotherapy," said Patricia Ernst, PhD, co-director of the Cancer Mechanisms Program of the Norris Cotton Cancer Center and an associate professor in Genetics at the Geisel School of Medicine.

The study focused on a pathway regulated by a gene called MLL1 (for Mixed Lineage Leukemia). Ernst served as principal investigator; Bibhu Mishra, PhD, as lead author.

When the MLL1 gene is damaged, it can cause leukemia, which is a cancer of the blood, often occurring in very young patients. Researchers found that the normal version of the gene controls many other genes in a manner that maintains the production of blood cells.

"This control becomes chaotic when the gene is damaged or 'broken' and that causes the normal blood cells to turn into leukemia," said Ernst.

The researchers showed that the normal gene acts with a partner gene called MOF that adds small "acetyl" chemical modification around the genes that it controls. The acetyl modification acts as a switch to turn genes on. When this function is disrupted, MLL1 cannot maintain normal blood stem cells.

The researchers also found that a gene called Sirtuin1 (more commonly known for controlling longevity) works against MLL1 to keep the proper amount of "acetyl" modifications on important stem cell genes. Blood cancers involving MLL1, in contrast, do not have this MOF-Sirtuin balance and place a different chemical modification on genes that result in leukemia.

Blood stem cells also represent an important therapy for patients whose own stem cells are destroyed by chemotherapy. This study also reveals a new way to treat blood stem cells from donors that would expand their numbers.

"These finding suggest that drugs that block Sirtuin1 may be combined with MLL1 blocking drugs in certain leukemia to both preserve stem cells that make normal blood at the same time as killing leukemia cells," said Ernst.

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Epigenetic mechanisms distinguishing stem cell function, blood cancer decoded

Stem cell progeny tell their parents when to turn on

By Stem Cell Medical Center

May 09, 2014 A signal from Transit-Amplifying Cells (TACs) activates stem cells in the hair follicle, researchers have found. Both types of cells appear in green (top), with TACs clustered lower down. The researchers identified the signal as Sonic Hedgehog. In experiments, such as this one (bottom), they disabled the signal, interfering with hair growth and regeneration.

(Phys.org) Stem cells switch off and on, sometimes dividing to produce progeny cells and sometimes resting. But scientists don't fully understand what causes the cells to toggle between active and quiet states.

New research in Elaine Fuchs' Laboratory of Mammalian Cell Biology and Development focused on stem cells in the hair follicle to determine what switches them on. The researchers found cells produced by the stem cells, progeny known at Transit-Amplifying Cells or TACs, emit a signal that tells quiet hair follicle stem cells to become active.

"Many types of mammalian stem cells produce TACs, which act as an intermediate between the stem cells and their final product: fully differentiated cells in blood, skin and elsewhere," says Ya-Chieh Hsu, who conducted the research while as a postdoc in the lab and will soon move to Harvard University. "In the past, TACs were seen as a population of cells that sat by passively cranking out tissues. No one expected them to play a regulatory role."

Hsu and Fuchs went a step further to identify the signal sent out by the TACs. They pinpointed a cell-division promoting protein called Sonic Hedgehog, which plays a role in the embryonic development of the brain, eyes and limbs.

Stem cells are medically valuable because they have the potential to produce a number of specialized cells suitable for specific roles. Stem cells' production of these differentiated cells is crucial to normal maintenance, growth and repair. Many tissues have two populations of stem cells: one that divides rarely, known as the quiescent stem cells, and another that is more prone to proliferate, known as primed stem cells. Regardless of their proliferation frequency, most stem cells in humans do not directly produce differentiated progeny cells; instead, they give rise to an intermediate proliferating population, the TACs.

The hair follicle, the tiny organ that produces a hair, forms a narrow cavity down into the skin. It cycles between rounds of growth, destruction and rest. When entering the growth phase, the primed stem cell population is always the first to divide and generates the TACs clustered lower down in the hair follicle. Primed stem cell proliferation sets the stage for the next round of hair growth, a process which ensures hairs are replaced as they are lost over time. Proliferating TACs produce the hair shaft, as well as all the cells surrounding the hair underneath the skin, which make up the follicle itself.

At the outset, Hsu and Fuchs suspected a role for both the TACs and for Sonic Hedgehog in hair regeneration.

"We noticed that the primed stem cell population gets activated early and makes the TACs, while the quiescent stem cell population only becomes activated once TACs are generated. This correlation prompted us to look for a signal that is made by the TACs. Sonic Hedgehog is that signal, as we went on to demonstrate," explained Fuchs.

In experiments described this week in Cell, Hsu disabled TACs' ability to produce the Sonic Hedgehog protein by knocking out the gene responsible in the hair follicles of adult mice. As a result, the proliferation of hair follicle stem cells and their TACs are both compromised. They further showed that it is the quiescent stem cell population which requires Sonic Hedgehog directly for proliferation.

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Stem cell progeny tell their parents when to turn on

Production of synthetic SIRT1 as a dietary supplement may help prolong life, states Chemist Direct

By Uncategorized

(PRWEB UK) 9 May 2014

Over the course of the human life span the body ages and becomes less able to repair itself, allowing it to become more prone to disease and illness. In the ever developing field of scientific discovery researchers have become intrigued with the concept of finding a way to slow down age-related diseases and prolonging life through the use of medicine. Since the Japanese scientist Shinya Yamanaka (http://bit.ly/1kWb20u) first discovered iPS cells in adult tissue and pioneered mature cell regeneration, this field in medicine has become one of the most rapidly developing fields in biomedicine.

A research team at the National Institute on Ageing at the National Institutes of Health in the US has discovered a promising strategy to arrest ageing by looking at a chemical called SRT1720 which activates a particular protein called Sirtuin 1 (SIRT1). Previous research has demonstrated that activating SIRT1 can have health benefits in various organisms, and it has been proposed as an anti-ageing protein. This study, published in the March edition of Research Journal: Cell (http://bit.ly/1od2gS5) focused on comparing the lifespan, health and diseases of mice fed the same diet, but with or without the addition of a SRT1720.

Overall they found mice fed a normal diet but with the supplement had a longer natural lifespan on average (about five weeks longer). During their lifetime, additional tests also suggested they had improved muscle function and coordination, improved metabolism, improved glucose tolerance, decreased body fat and cholesterol. All in all this suggests that giving the mice this supplement could protect them from the equivalent of metabolic syndrome, a series of risk factors associated with conditions such as heart disease and type 2 diabetes.

A study published today in the journal Stem Cell Reports (http://bit.ly/1hBSDF6) and carried out by the Spanish National Cancer Research Centre's Telomeres and Telomerase Group, reveals that the SIRT1 protein is needed to lengthen and maintain telomeres during cell reprogramming. SIRT1 also guarantees the integrity of the genome of stem cells that come out of the cell reprogramming process; these cells are known as iPS cells (induced Pluripotent Stem cells).

The nature of iPS cells, however, is causing intense debate. The latest research shows that chromosome aberrations and DNA damage can accumulate in these cells. "The problem is that we don't know if these cells are really safe," says Mara Luigia De Bonis, a postdoctoral researcher who has done a large part of the work. http://bit.ly/1m5gRgb

Researchers did not look at whether SIRT1 may cause side effects or complications so it is currently unclear whether SIRT1 would be safe in humans, let alone effective, but this interesting research has opened doors to pharmaceutical companies to develop dietary supplements that can help provide anti-aging pills, especially those who suffer hereditary degenerative diseases. These ongoing scientific studies will help shed light on how cell reprogramming guarantees the healthy functioning of stem cells. This knowledge will help to overcome barriers that come out of the use of iPS cells so they may be used in regenerative medicine.

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Production of synthetic SIRT1 as a dietary supplement may help prolong life, states Chemist Direct

First stem cell trial for stroke shows lasting benefits

By Stem Cell Treatment

People who received the world's first stem cell treatment for strokes have shown measurable reductions in disability and handicap a year after the injection into their damaged brains.

Some can move limbs and manage everyday tasks that were impossible before they received an injection of neural progenitor stem cells, which were clones of cells originally taken from the cortex of a donated fetus.

Apart from physical rehabilitation, there are few treatments for people left severely disabled by a stroke. Demand for more options is high, with 800,000 new cases each year in the US and 150,000 in the UK.

"We're encouraged, and it's a nice progressive piece of news," says Michael Hunt, the chief executive officer of ReNeuron, the company in Guildford, UK, that developed the treatment. "We must be circumspect, but we are seeing what seems to be a general trend towards improvement in a disparate group of patients," he says.

ReNeuron presented its latest results on the first 11 patients on 7 May in Nice, France, at the 23rd European Stroke Conference. They build on interim findings released last year.

The patients in the PISCES trial (Pilot Investigation of Stem Cells in Stroke) had all suffered their strokes at least six months before treatment and were all chosen because their symptoms had plateaued, making any improvements more likely to be the result of treatment.

There were improvements in median scores on all five scales used to measure the patients' recovery.

On a score that measures quality of life from 0 to 100, patients began with a median score of 45, but within a year this had risen by 18 points, a 40 per cent improvement.

Rankin Scores, which grade disability and handicap from healthy (0) to dead (6) improved from a median of 3 at the start to 2 for four of the patients, although the rest remained the same. "That's equivalent to taking a patient down a whole level of dependency, and equates to a 20 per cent improvement," says Hunt. Scores on all the other three scales were higher at 12 than at three months, suggesting the improvements were continuing.

The company is now actively recruiting for a second, larger trial in 41 people. They will be recruited sooner after their strokes within two to three months in the hope that earlier treatment will prevent some of the irreversible scarring. It will also deploy a harder but more objective measure of improvement in which patients have to try lifting a wooden block onto a platform. Hunt expects full results by the end of 2015.

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First stem cell trial for stroke shows lasting benefits

Son's successful stem cell transplant best Mother's Day present

By Stem Cell Treatment

NASHVILLE, Tenn. - Carrie Yokley and her family stayed at the Ronald McDonald House in Nashville while her son Ryan received lifesaving treatment.

On Friday afternoon, Yokley said her prayers were answered. Doctorssaid her sons stem cell transplant was a success, curing him of two diseases, Burton's and Crohn's.

She said that is the best Mothers Day gift she could have hoped for.

You think your kids are the best gift you can get, but then you get a gift like this, [he gets] a second chance to be a little boy, said Yokley.

Carrie Yokley will celebrate Mothers Day at the Ronald McDonald House, along with 32 other mothers going through a similar experience.

It's just a nice time for them to put aside the worries they have about their child's illness and celebrate being a mother and getting to be with their children, said Heather Powell, with the Ronald McDonald House Charities.

Ryan cannot be around other people until his immune system improves. Yokley said Ryan felt bad that he could not do more with his mother on the special day.

She assured him, this Mothers Day she received everything she wanted.

I said we're together, I have you all, that's the best Mother's Day present ever, said Yokley.

The Ronald McDonald House Charities of Nashville provides a home away from home for families of critically ill children receiving care at Nashville area hospitals.

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Son's successful stem cell transplant best Mother's Day present

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