Monthly Archive for June, 2009Page 2 of 6

In muscle stem cells age matters

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Body Builder Muscle Man
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CHICAGO (Reuters) – A new understanding of the genes that make muscle cells may change the way researchers think about stem cell transplants for muscular dystrophy and muscle injuries, U.S. researchers said on Wednesday.

In a surprise finding, they said genes important for forming muscle cells in embryos and newborns are not normally active in adult stem cells.
And researchers hoping to use muscle stem cells in stem-cell transplant therapies should not assume genes that control early muscle development serve the same purpose in repairing adult muscle, Christoph Lepper and colleagues at the Carnegie Institution in Baltimore reported in the journal Nature.

Earlier studies have shown that two genes — Pax3 and Pax7 — control cells that give rise muscle in embryos, and Pax7 also helps build muscle in newborn mice.
To get a better understanding of their function, Lepper and colleagues studied these genes at various stages of development in live mice.

“I thought that if they are so important in the embryo, they must be important for adult muscle stem cells,” Lepper said in a statement.
The team used genetic engineering to suppress both the Pax3 and Pax7 genes in adult muscle stem cells, and they found that adult stem cells were still able to function normally.

“I was totally surprised to find that the muscle stem cells are normal without them,” Lepper said
The researchers then looked at whether the same was true in injured muscles, when muscle stem cells go to work making new muscle tissue.

To study this, they injured mouse leg muscles between the knee and ankle, and found the muscle stem cells were able to make new muscle, even without the two key embryonic muscle stem cell genes.
The team said the embryonic muscle cell genes appear to only be active in mice within the first three weeks after birth. After that, they believe the genes go quiet and allow a different set of genes to take over.

Finding those genes will be important as scientists pursue new treatments for diseases like muscular dystrophy, a genetic, degenerative disease that affects voluntary muscles, they said.
And they said teams should look at other types of stem cells to see how age might affect their properties, and they should take age of stem cells into account in transplant-based treatments.

from Reuters

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ITALY – Embryonic stem cells: Waldensian church doubles “eight per thousand” allocation to fund stem cell research.

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The Waldensian community in Italy has decided that next year, it will double its so-called “eight per thousand” allocation from the Italian government to embryonic stem cell research projects, increasing funds from 50,000 euros in 2007 (declared in 2004) to 100,000 euros in 2008 (declared in 2005), said Maria Bonafede, the moderator of the Waldensian executive committee, presenting the group’s 2009 campaign to allocate “eight per thousand” funds. “Eight per thousand” is an Italian law in which 0.8% of the personal income tax collected is redistributed to the Italian government and various religious groups.

With this mechanism, the Waldensian and Methodist churches received 1.6% of the total funds in 2008, totaling 6.9 million euros. Two stem cell projects are sponsored by the Waldensians, out of the 250 projects financed abroad and in Italy thanks to their “eight per thousand” revenue. The first is a study at the University of Bologna to which the Waldensian church destined 50,000 euros in 2007, which increased to 100,000 euros in 2008. The other project is an embryonic stem cell study at the University of Milan. “In Italy, this type of research is very expensive,” explained Paolo Naso, the head of advertising for the Waldensian community’s eight per thousand funding program, “and money is needed to buy stocks of embryonic cells from abroad”.

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In search of stem cells with a perfect tissue match

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The extensive research on stem cells has revolutionised the way life-threatening diseases like leukaemia and aplastic anaemia can be treated.
But there are several steps before these diseases can be treated using stem cells.

To begin with, the Human Leukocyte Antigen (HLA)-typing of the patient is done. Doctors then get into the process of finding a matched donor from the computerised list made available to them by National Marrow Donor Programme (NMDP), U.S., and New York Cord Blood Bank.
If registration of potential bone marrow donors has been in place for a long time, the emergence of a number of cord blood banks, both public and private, which store the stem cells has gone a long way in helping doctors.

Finding a match is just the first step. However, it takes at least three months to procure matched bone-marrow stem cells. It takes just two weeks in the case of cord blood stem cells.
The three-month waiting period in the case of bone marrow arises as locating the matched donor very often becomes difficult.

It requires a minimum of one to three working days to import the stem cells once the match has been found.
“We transfuse blood and platelets to aplastic anaemia patients to sustain them till such time matched stem cells are located, procured and transplanted,” said Dr. Revathy Raj, Consultant Paediatric Haemato Oncologist, Apollo Speciality Hospital, Chennai. “In the case of leukaemia, patients undergo a cycle of chemotherapy in the interim period.”

An important point worthy of mention is that the bone marrow donor is not required to come to the hospital where the patient is, but rather could go to a nearest hospital in the U.S. to donate his stem cells.
In India there are not enough registered bone marrow donors, nor are there proper facilities to harvest bone marrow. Hence the bone marrow cells have to be obtained from organisations like NMDP. The lack of adequate number of donors also results in very slim chances of finding a match in India.

India fares better in the case of cord blood banks. India has two public banks — Reliance in Mumbai and Jeevan Stem Cell Bank in Chennai. But even these banks have only a handful of units. This makes the chances of finding a match very remote.
Though there are a good number of private cord blood banks in the country, they are of little use to the public. Stem cells banked in these places are made available only to the immediate relative of the donor.

from The Hindu

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Thalassemia cured using cord blood stem cells

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Bond strengthened: Eight-year-old Thamirabharuni, holding her brother who donated the stem cells, did not suffer from rejection or graft versus host disease as the tissue match was perfect - Photo: V. Ganesan

Bond strengthened: Eight-year-old Thamirabharuni, holding her brother who donated the stem cells, did not suffer from rejection or graft versus host disease as the tissue match was perfect - Photo: V. Ganesan

Eight-year-old Thamirabharuni and her one-year-old brother Pugazhendhi share a special kind of bond not commonly seen among siblings. Thanks to her brother, Thamirabharuni no longer suffers from thalassemia disease.

The stem cells transplanted in March helped her get rid of thalassemia. And hundred days after the procedure, one can safely say that her disease has been cured.
The stem cells that were transplanted came from two different sources — her brother’s cord blood, which was harvested during the time of his birth, and his bone marrow. Stem cells from the bone marrow had to be transplanted as there was insufficient number of stem cells in Pugazhendhi’s cord blood.

In the absence of cord blood stem cells, about 200 ml of bone marrow would have been required. It is difficult to get this quantity of bone marrow from a nine-month-old baby.
The cord blood was collected by and stored at Chennai based LifeCell International Pvt. Ltd., a private cord blood bank.

Risk of infection

So is it all over? “One has to be still careful. There is a risk of infection till the end of the first year [after transplantation],” said Dr. Revathy Raj, Consultant Paediatric Haemato Oncologist, Apollo Speciality Hospital, Chennai. Dr. Raj had done the transplantation for Thamirabharuni and two other cord blood transplantations for thalassemia before this.
The fact that patients are on immuno suppressing drugs for one year makes them vulnerable to infections. The risk of rejection of the transplanted stem cells, and the graft versus host disease (GVHD) reduce with time.

Thalassemia arises when red blood corpuscles (RBC) production is defective. A person suffers from the disease only when he inherits a defective gene from both parents. He becomes a carrier when he inherits a defective gene from only one parent. The diseased person has to undergo blood transfusion once every month for the rest of his life.

Gold standard

Though stem cells separated from bone marrow have been used for more than 30 years to treat thalassemia, and is a gold standard in treating the disease, cord blood stem cells are slowly becoming an attractive alternative.
Contrary to what is projected by some cord blood banks, doctors are very reluctant to use cord blood stem cells to treat thalassemia in the absence of a full tissue match.

Perfect match

“We need a 6/6 [perfect match] for thalassemia. Even a 5/6 match is not sufficient,” asserted Dr. Raj. And doctors refrain from using stem cells from unrelated donors, even if there is a perfect match.

Apart from infections, there are two major challenges from transplantation — graft versus host disease (GVHD) and rejection of the donated stem cells. “There is a 30 per cent chance of having graft versus host disease even when it is from a fully matched related (sibling) donor.” This risk increases to 50 per cent when it is from an unrelated donor, even if there is 6/6 tissue match.

Rejection rate becomes an issue even when there is a perfect tissue match. According to her, in the case of thalassemia, the rejection rate can be up to 20 per cent even with related donors, and up to 40 per cent in the case of unrelated donors.
But why should rejection and GVHD be an issue at all when there is a perfect 6/6 tissue match, and why should it be so high when stem cells are from unrelated donors?

Minor HLAs not tested

“There are several minor HLA antigens that are not tested. So if we use stem cells from people belonging to some other ethnic background, there are greater chances of [minor] HLA differences,” Dr. Raj stressed. “And this causes rejection and GVHD.”
In general, greater the tissue match and higher the stem cell count in cord blood, lesser are the chances of rejection and GVHD.

“So why undertake procedures that are risky when thalassemia can be treated through monthly transfusions,” she noted.
Private banking of cord blood for use by the family therefore becomes important when one of the siblings is suffering from a disease that can be cured using it.

Case for public banking

Despite the risk of rejection and GVHD, a less than perfect sample can be used to treat children suffering from life threatening diseases such as leukaemia and aplastic anaemia. This is where public cord blood banking gains significance.
There is a strong case for promoting public banks as depending solely on bone marrow samples will not be wise.

Even if a perfectly matched bone marrow donor is found, chances are that the person may no longer be interested in donating.
Collecting cord blood samples is easy, the number of samples that can be banked is limited only by resources, and samples can be made available at very short notice.

from  The Hindu

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GREAT BRITAIN – Embryonic stem cells cure blindness in an hour

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After much hope and controversy, for the first time stem cells have proven to have the ability to cure a disease. The news comes from a study on age-related macular degeneration (AMD) of the retina, the most common cause of blindness in individuals over the age of 50. The Sunday Times reports that the treatment was developed by a group of British researchers, who say that in the next six to seven years the treatment will become a routine operation, which will not last more than an hour. The treatment involves the replacement of a layer of degenerated cells with new cells created using embryonic stem cells, primitive cells that are able to transform into any type of human tissue.

AMD strikes the central area of the retina, the macula, which progressively deteriorates. Cloned retina cells are placed on an artificial membrane inserted into the posterior retina. The research was conducted by the department of ophthalmology of the University College of London and Morfields Hospital. Ethical controversy is inevitable because in order to create this type of stem cells embryos are used, which is explicitly allowed by British legislation. American pharmaceutical group Pfizer, said the Times, is supporting the study.

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Stem Cells Used to Grow Hearts

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From left to right: A normal pig heart, a pig heart after being decellularised, the pig heart prepared for recellularisation. Photos courtesy of the University of Minnesota.

In a medical first, University researchers have created a beating heart in the laboratory. Using detergents, they stripped away the cells from rat hearts until only the nonliving matrix, or “skeleton,” was left; they then repopulated the matrix with fresh heart cells.

If perfected, the technique may be used someday to generate new hearts for patients. In the United States alone, about 5 million people live with heart failure, 550,000 new cases are diagnosed every year, and 50,000 die waiting for a donor heart.

“The results were a home run,” says Doris Taylor, director of the University’s Center for Cardiovascular Repair and a principal investigator on the study. “We knew that cell therapy–that is, transplanting cells into [a patient's damaged] heart–is not a panacea. So we started thinking, ‘Is there a way to use cells to engineer heart tissue?’”

The idea, she says, is to create whole new blood vessels or organs by implanting a patient’s own cells into a matrix derived from a donor organ. This approach ought to bypass the problem of organ rejection because the matrix, being devoid of cells, shouldn’t provoke an immune response. Even if it did, the new cells would create a fresh matrix of their own, which would turn off the immune response and free patients from the need to take immunosuppressive drugs.

The process, called whole organ recellularization, can be done “with virtually any organ,” Taylor says.

A simple plan

The main hurdle in creating new hearts wasn’t finding the right cells but recreating the vastly complex architecture of the heart, Taylor explains. In puzzling it over, she and Harald Ott, a research associate in the center (now a surgical resident at Harvard Medical School and first author of the study), hit on a way to get nature to solve the problem for them.

To remove cells from fresh rat hearts, the researchers pumped solutions of detergents through the network of blood vessels that normally nourish the organ. The treatment popped all the cells like balloons and washed away the debris, leaving the matrix of protein fibers that form the backbone of a living heart’s connective tissue. It’s called the extracellular matrix, or ECM.

http://brightcove.vo.llnwd.net/d7/unsecured/media/981571807/981571807_25285320001_rat-heart-.flv

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