See Inside Mar 19, 2013 |By Christine Gorman

Richard Clark, NIH

Researchers are now experimenting with stem cellsprogenitor cells that can develop into many different types of tissueto coax the bodies of a few individuals to heal themselves. Some of the most advanced clinical trials so far involve treating congestive heart disease and regrowing muscles in soldiers who were wounded in an explosion. But new developments are happening so quickly that investigators have come up with a new nameregenerative medicineto describe the emerging field.

Many of the stem cells being studied are referred to as pluripotent, meaning they can give rise to any of the cell types in the body but they cannot give rise on their own to an entirely new body. (Only the earliest embryonic cells, which occur just after fertilization, can give rise to a whole other organism by themselves.) Other stem cells, such as the ones found in the adult body, are multipotent, meaning they can develop into a limited number of different tissue types.

One of the most common stem cell treatments being studied is a procedure that extracts a few stem cells from a person's body and grows them in large quantities in the laboratorywhat scientists refer to as expanding the number of stem cells. Once a sufficient number have been produced in this manner, the investigators inject them back into the patient.

The bone marrow is a rich source of adult stem cells, containing both the hematopoietic stem cells that give rise to the various types of blood and the so-called mesenchymal cells, which can develop into bone, cartilage and fat. Mesenchymal cells are found in the bone marrow and various other places in the body, although whether all mesenchymal stem cells are truly interchangeable irrespective of origin is unclear.

Scientific American spoke with Mahendra Rao, director of the Center for Regenerative Medicine at the National Institutes of Health in Bethesda, Md., to get a sense of the sorts of new developments that might occur in regenerative medicine in the next five years or so.

[An edited transcript of the interview follows.]

Why is there so much excitement about regenerative medicine? You could say that medicine up until now has been all about replacements. If your heart valve isn't working, you replace it with another valve, say from a pig. With regenerative medicine, you're treating the cause and using your own cells to perform the replacement. The hope is that by regenerating the tissue, you're causing the repairs to grow so that it's like normal.

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What's Next for Stem Cells and Regenerative Medicine?

21.Spinal Cord Injury(T5-6) Treated by Stem Cell Therapy(Before)
Patient with T5-6 spinal cord injury: condition before treatment Before treatment, sensation remains only above the waist. Sweating remains only in the upper...

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21.Spinal Cord Injury(T5-6) Treated by Stem Cell Therapy(Before) - Video

Celltex Therapeutics of Houston ceased treatment patients in the U.S. last year after a warning from regulators, and will now send patients for treatments to Mexico

Flickr/GE Healthcare

US citizens who had pinned their hopes on a company being able to offer stem-cell treatments close to home will now need to travel a little farther. Celltex Therapeutics of Houston, Texas, stopped treating patients in the United States last year following a warning from regulators. A 25 January e-mail to Celltex customers indicates that the firm will now follow in the footsteps of many other companies offering unproven stem-cell therapies and send its patients abroad for treatment but only to Mexico.

The stem-cell treatments offered by Celltex involved extracting adult stem cells from a patient, culturing them and then reinjecting them in a bid to replenish damaged tissue. It had been offering the treatment for more than a year with one of its high-profile customers being Texas governor, Rick Perry when the US Food and Drug Administration (FDA) wrote to the company on 24 September 2012 advising it that the stem cells it harvested and grew were more than minimally manipulated during Celltex's procedures. As such, the FDA regarded the cells as drugs, which would require the agency's approval to be used in treatments. The FDA also warned that Celltex had failed to address problems in its cell processing that inspectors from the agency had identified in an April 2012 inspection of its cell bank in Sugar Land, Texas. Shortly after it received the letter, Celltex stopped injecting stem cells into patients.

For customers who still had cells banked at Celltex and were wondering how to get them out, things became more chaotic when Celltex and RNL Bio, a company based in Seoul, South Korea, which operated the processing center and bank in Sugar Land, sued each other over financial disagreements. Celltex had to issue a restraining order just to gain access to the cells.

The January e-mail from Celltex reassures customers that their cells are safely stored in a facility in Houston and adds: We anticipate that we will be able to offer our stem cell therapy services to physicians in Mexico starting very soon! The e-mail also says that the company is building a new laboratory in Houston, to be opened in March.

Celltex adds that it will carry out an FDA-approved clinical trial, to start shortly after a March meeting with the FDA, pending a positive review from the regulator. However, the company had said in a 25 October e-mail to patients that it would start such a trial within two months and that patient enrolment could begin in late November.

Leigh Turner, a bioethicist at the University of Minnesota in Minneapolis, says that the move to Mexico is "not surprising", given the companys difficulties in the United States.

As Celltex's stem culturing and banking technology was licensed from RNL Bio, it is also not clear whether it has the expertise needed to launch a clinical trial on its own, says Turner. "It would have to build a stem-cell company from the ground floor up. I wouldnt say it is anywhere near the starting line."

Celltex did not respond to questions about how it would ship stem cells to Mexico or how it would perform the clinical research needed to seek FDA approval.

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Controversial Stem Cell Company Moves Treatment out of U.S.

BOSTON -

A bone marrow transplant could be a life-saving move for a little girl from Chester.

Keith McGilvery visited her at Boston Children's Hospital Tuesday and found out she's not the only young Vermonter who's sick on her floor. There are two kids from Vermont-- one from Chester and the other from Colchester. They're neighbors at Children's Hospital hoping that their transplants will make them better.

Tuesday, we visited Lindsey Sturtevant, she's the 12-year-old who just received a second bone marrow transplant to fight off a pre-leukemia condition that's done a number on her blood cells.

During our visit, we learned that Colchester Middle Schooler Le'Ondre Brockington is in the hospital bed next door. The 13-year old is fighting a rare form of acute myeloid leukemia. He's been in the hospital for seven months and his mom says every day has been a battle. Both families are thankful to their transplants.

Lindsey's doctor, Christine Duncan of the Dana-Farber Cancer Institute and Boston Children's Hospital, talked with us about what's involved if you decide to donate.

"There are lots of different ways that we collect stem cells. Some are directly from the bone, some are from your blood, most often it is a blood-type donation. For people that are really interested, they can look at the national marrow donor program which is the program that helped us find a donor for Lindsey," Dr. Duncan said.

Matches don't always come from family; Lindsey's first donor came from a 42-year-old woman in Europe and the second came from a 23-year-old man.

Le'Ondre's bone marrow donation came from a 33-year-old man.

For more information on becoming a donor:

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Sick Vt. kids highlight need for bone marrow donors

Research from Karolinska Institutet in Sweden suggests that the expression of the so called MYC gene is important and necessary for neurogenesis in the spinal cord. The findings are being published in the journal EMBO Reports.

The MYC gene encodes the protein with the same name, and has an important role in many cellular processes such as proliferation, metabolism, cell death and the potential of differentiation from immature stem cells to different types of specialized cells. Importantly it is also one of the most frequently activated genes in human cancer.

Previously MYC has been shown to promote proliferation and inhibit differentiation in dissociated cells in culture. However, in the current study researchers demonstrate that in the intact neural tissue from chickens, MYC promotes differentiation of neural cells rather than their proliferation.

"We hope that this news knowledge can be important for developing future strategies to promote nerve cell development, for example in patients with spinal cord injuries," says principal investigator Marie Arsenian Henriksson, professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.

Story Source:

The above story is based on materials provided by Karolinska Institutet. Note: Materials may be edited for content and length.

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New findings on neurogenesis in spinal cord

Inhibition of a prostaglandin with nonsteroidal anti-inflammatory drugs has been found to cause stem cells to leave marrow, where they could be harvested for patients with blood disorders

Tino Soriano/National Geographic Society/Corbis

Aspirin-like drugs could improve the success of stem-cell transplants for patients with blood or bone-marrow disorders, a study suggests. The compounds coax stem cells from bone marrow into the bloodstream where they can be harvested for use in transplantation and they do so with fewer side effects than drugs now in use.

For patients with blood disorders such as leukemia, multiple myeloma or non-Hodgkins lymphoma, transplantation of haematopoietic stem cells precursor cells that reside in the bone marrow and give rise to all types of blood cell can be an effective treatment.

Previous work has shown that prostaglandin E2, or PGE2, a lipid known to regulate multiple bodily reactions including pain, fever and inflammation, also has a role in keeping stem cells in the bone marrow. In the latest study, researchers show that in mice, humans and baboons, inhibition of PGE2 with non-steroidal anti-inflammatory drugs (NSAIDs) causes stem cells to leave the bone marrow.

Releasing the stem cells The team gave baboons and humans an NSAID called meloxicam. They saw a subsequent increase in the numbers of haematopoietic stem cells in the bloodstream.

The researchers think that the departure of stem cells is caused by the disturbance of a group of bone-forming cells called osteoblasts. These cells secrete a protein called osteopontin that hooks the stem cells to the bone marrow. Inhibiting PGE2 would disrupt the production of osteopontin.

At present, doctors use a drug called filgrastim to mobilize haematopoietic stem cells in donors or in patients undergoing autotransplantation (in which they receive their own stem cells). In patients with multiple myeloma or non-Hodgkins lymphoma, however, and in some donors, stem cells dont mobilize well with filgrastim and other drugs in its class. Using NSAIDs such as meloxicam could enhance filgrastims efficacy, says lead author Louis Pelus of the Indiana University School of Medicine in Indianapolis. The study appears in Nature.

Meloxicam also has comparatively few side effects, says Pelus. He and his colleagues found that other NSAIDs, including aspirin and ibuprofen, can also mobilize haematopoietic stem cells, but these drugs can cause gastrointestinal upset in patients. PGE2 controls the secretion of hydrochloric acid in the stomach, and when you block that youve reduced your ability to control acid secretion. Meloxicam doesnt do that as badly as many of the other [drugs] do, he says.

For Charles Craddock, director of the blood and marrow transplant unit at the Queen Elizabeth Hospital in Birmingham, UK, the results might also hold clues about how to mediate the tricky process of getting cells back to the bone marrow once transplanted. If youre beginning to understand what mediates cells moving out, you might be able to understand what mediates cells moving in. If you can make bone marrow more sticky, when you put cells back, you might be able to keep them in.

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Painkillers Could Prove Helpful in Stem-Cell Transplants

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HIV attacks a type of immune cell known as a T cell (shown here) using a protein encoded by the CCR5 gene.

A clinical trial has shown that a gene-editing technique can be safe and effective in humans. For the first time, researchers used enzymes called zinc-finger nucleases (ZFNs) to target and destroy a gene in the immune cells of 12 people with HIV, increasing their resistance to the virus to the virus. The findings are published today in The New England Journal of Medicine1.

This is the first major advance in HIV gene therapy since it was demonstrated that the Berlin patient Timothy Brown was free of HIV, says John Rossi, a molecular biologist at the Beckman Research Institute of the City of Hope National Medical Center in Duarte, California. In 2008, researchers reported that Brown gained the ability to control his HIV infection after they treated him with donor bone-marrow stem cells that carried a mutation in a gene called CCR5. Most HIV strains use a protein encoded by CCR5 as a gateway into the T cells of a hosts immune system. People who carry a mutated version of the gene, including Brown's donor, are resistant to HIV.

But similar treatment is not feasible for most people with HIV: it is invasive, and the body is likely to attack the donor cells. So a team led by Carl June and Pablo Tebas, immunologists at the University of Pennsylvania in Philadelphia, sought to create the beneficial CCR5 mutation in a persons own cells, using targeted gene editing.

The researchers drew blood from 12 people with HIV who had been taking antiretroviral drugs to keep the virus in check. After culturing blood cells from each participant, the team used a commercially available ZFN to target the CCR5 gene in those cells. The treatment succeeded in disrupting the gene in about 25% of each participants cultured cells; the researchers then transfused all of the cultured cells into the participants. After treatment, all had elevated levels of T cells in their blood, suggesting that the virus was less capable of destroying them.

Six of the 12 participants then stopped their antiretroviral drug therapy, while the team monitored their levels of virus and T cells. Their HIV levels rebounded more slowly than normal, and their T-cell levels remained high for weeks. In short, the presence of HIV seemed to drive the modified immune cells, which lacked a functional CCR5 gene, to proliferate in the body. Researchers suspect that the virus was unable to infect and destroy the altered cells.

They used HIV to help in its own demise, says Paula Cannon, who studies gene therapy at the University of Southern California in Los Angeles. They throw the cells back at it and say, Ha, now what?

In this first small trial, the gene-editing approach seemed to be safe: Tebas says that the worst side effect was that the chemical used in the process made the patients bodies smell bad for several days.

The trial isnt the end game, but its an important advance in the direction of this kind of research, says Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. Its more practical and applicable than doing a stem-cell transplant, he says, although it remains to be seen whether it is as effective.

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Gene-editing method tackles HIV in first clinical test

Engineering a patients own immune cells to resist HIV could eliminate the need for lifelong antiretroviral therapies.

The immune cells of HIV patients can be genetically engineered to resist infection, say researchers. In a small study in humans, scientists report that by creating a beneficial mutation in T cells, they may be able to nearly cure patients of HIV.

In a study published in the New England Journal of Medicine on Wednesday, researchers report that they can use genome editing to re-create the rare mutations responsible for protecting about 1 percent of the population from the virus in infected patients. They report that some of the patients receiving the genome-modifying treatment showed decreased viral loads during a temporary halt of their antiretroviral drugs. In one patient, the virus could no longer be detected in his blood.

Zinc-finger nucleases are one of a few genome-editing tools that researchers use to create specific changes to the genomes of living organisms and cells (see Genome Surgery). Scientists have previously used genome-editing techniques to modify DNA in human cells and nonhuman animals, including monkeys (see Monkeys Modified with Genome Editing). Now, the NEJM study suggests the method can also be safely used in humans.

From each participating patient, the team harvested bone marrow stem cells, which give rise to T cells in the body. They then used a zinc finger nuclease to break copies of the CCR5 gene that encodes for proteins on the surface of immune cells that are a critical entry point of HIV. The stem cells were then infused back into each patients bloodstream. The modification process isnt perfect, so only some of the cells end up carrying the modification. About 25 percent of the cells have at least one of the CCR5 genes interrupted, says Edward Lanphier, CEO of Sangamo Biosciences, the Richmond, California, biotech company that manufactures zinc finger nucleases.

Because the cells are a patients own, there is no risk of tissue rejection. The modified stem cells then give rise to modified T cells that are more resistant to infection by HIV, say the researchers.

One week after the infusion, researchers were able to find modified T cells in the patients blood. Four weeks after the infusion, six of the 12 patients in the study temporarily stopped taking their antiretroviral drugs so the researchers could assess the effect of the genome-editing treatment on the amount of the virus in the patients bodies. In four of these patients, the amount of HIV in the blood dropped. In one patient, the virus could no longer be detected at all. The team later discovered that this best responder had naturally already had one mutated copy of the CCR5 gene.

Patients who carry one broken copy of the CCR5 progress to AIDS more slowly than those who dont, says Bruce Levine, a cell and gene therapy researcher at the University of Pennsylvania School of Medicine and coauthor on the study. Because all of the cells in that best-responder patient already carried one disrupted copy of CCR5, the modification by the zinc finger nuclease led to T cells with no functional copies of the gene. That means the cells are fully resistant to HIV infection. The team is now working to increase the number of immune cells that end up carrying two broken copies of CCR5.

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Can Gene Therapy Cure HIV?

Doctors in London have devised a way to reconstruct human ears and noses with stem cells taken from body fat, BBC News reported.

In a study published in the journal Nanomedicine, researchers from Great Ormond Street Hospital in London said theyve successfully used fat stem cells to grow cartilage in a laboratory setting. Using ear-shaped scaffolding to ensure that the stem cells grow into the desired shape, physicians said they hope to someday be able to implant lab-grown cartilage underneath a persons skin to correct facial abnormalities.

While more testing needs to be done before the technique is used in patients, researchers hope to use this method to help patients with conditions like microtia a congenital deformity that can leave a child with a missing or malformed ear. Currently, the only corrective procedure available to these children involves taking cartilage from the childs ribs a procedure that leaves permanent scaring and requires multiple surgeries.

"It would be the Holy Grail to do this procedure through a single surgery," study author Dr Patrizia Ferretti told BBC News."So, decreasing enormously the stress for the children and having a structure that hopefully will be growing as the child grows."

The researchers also said the technique could be useful in correcting cartilage damage in the nose.

Click for more from BBC News.

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Doctors grow ears, noses using body fat stem cells

Sir Ian Wilmut proposes an alternative method as a possible means of creating a mammoth--or a hybrid. Such research could lead to major biological discoveries and advances

Wikimedia Commons/Mammut

Editor's note: The following essay is reprinted with permission from The Conversation UK, an online publication covering the latest research.

By Ian Wilmut, University of Edinburgh

It is unlikely that a mammoth could be cloned in the way we created Dolly the sheep, as has been proposed following the discovery of mammoth bones in northern Siberia. However, the idea prompts us to consider the feasibility of other avenues. Even if the Dolly method is not possible, there are other ways in which it would be biologically interesting to work with viable mammoth cells if they can be found.

In order for a Dolly-like clone to be born it is necessary to have females of a closely related species to provide unfertilised eggs, and, if cloned embryos are produced, to carry the pregnancies. Cloning depends on having two cells. One is an egg recovered from an animal around the time when usually she would be mated.

In reality there would be a need for not just one, but several hundred or even several thousand eggs to allow an opportunity to optimise the cloning techniques. The cloning procedure is very inefficient. After all, after several years of research with sheep eggs, Dolly was the only one to develop from 277 cloned embryos. In species in which research has continued, the typical success rate is still only around 5% at best.

Elephant eggs

In this case the suggestion is to use eggs from elephants. Because there is a danger of elephants becoming extinct it is clearly not appropriate to try to obtain 500 eggs from elephants. But there is an alternative.

There is a considerable similarity in the mechanisms that regulate function of the ovaries in different mammals. It has been shown that maturation of elephant eggs is stimulated if ovarian tissue from elephants is transplanted into mice.

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Produce Woolly Mammoth Stem Cells, Says Creator of Dolly the Sheep

The breakthrough might set up another showdown about cloning for therapeutic purposes

OHSU Photos

From Nature magazine

It was hailed some 15 years ago as the great hope for a biomedical revolution: the use of cloning techniques to create perfectly matched tissues that would someday cure ailments ranging from diabetes to Parkinsons disease. Since then, the approach has been enveloped in ethical debate, tainted by fraud and, in recent years, overshadowed by a competing technology. Most groups gave up long ago on the finicky core method production of patient-specific embryonic stem cells (ESCs) from cloning. A quieter debate followed: do we still need therapeutic cloning?

A paper published this week by Shoukhrat Mitalipov, a reproductive biology specialist at the Oregon Health and Science University in Beaverton, and his colleagues is sure to rekindle that debate. Mitalipov and his team have finally created patient-specific ESCs through cloning, and they are keen to prove that the technology is worth pursuing.

Therapeutic cloning, or somatic-cell nuclear transfer (SCNT), begins with the same process used to create Dolly, the famous cloned sheep, in 1996. A donor cell from a body tissue such as skin is fused with an unfertilized egg from which the nucleus has been removed. The egg reprograms the DNA in the donor cell to an embryonic state and divides until it has reached the early, blastocyst stage. The cells are then harvested and cultured to create a stable cell line that is genetically matched to the donor and that can become almost any cell type in the human body.

Many scientists have tried to create human SCNT cell lines; none had succeeded until now. Most infamously, Woo Suk Hwang of Seoul National University in South Korea used hundreds of human eggs to report two successes, in 2004 and 2005. Both turned out to be fabricated. Other researchers made some headway. Mitalipov created SCNT lines in monkeys in 2007. And Dieter Egli, a regenerative medicine specialist at the New York Stem Cell Foundation, successfully produced human SCNT lines, but only when the eggs nucleus was left in the cell. As a result, the cells had abnormal numbers of chromosomes, limiting their use.

Monkeying around Mitalipov and his group began work on their new study last September, using eggs from young donors recruited through a university advertising campaign. In December, after some false starts, cells from four cloned embryos that Mitalipov had engineered began to grow. It looks like colonies, it looks like colonies, he kept thinking. Masahito Tachibana, a fertility specialist from Sendai, Japan, who is finishing a 5-year stint in Mitalipovs laboratory, nervously sectioned the 1-millimetre-wide clumps of cells and transferred them to new culture plates, where they continued to grow evidence of success. Mitalipov cancelled his holiday plans. I was happy to spend Christmas culturing cells, he says. My family understood.

The success came through minor technical tweaks. The researchers used inactivated Sendai virus (known to induce fusion of cells) to unite the egg and body cells, and an electric jolt to activate embryo development. When their first attempts produced six blastocysts but no stable cell lines, they added caffeine, which protects the egg from premature activation.

None of these techniques is new, but the researchers tested them in various combinations in more than 1,000 monkey eggs before moving on to human cells. They made the right improvements to the protocol, says Egli. Its big news. Its convincing. I believe it.

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Patient-Specific Human Embryonic Stem Cells Created by Cloning

The California Institute for Regenerative Medicine is rethinking its rules in the wake of a recent breakthrough involving the creation of stem cell lines from a cloned human embryo

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The announcement last month of a long-awaited breakthrough in stem-cell research the creation of stem-cell lines from a cloned human embryo has revived interest in using embryonic stem cells to treat disease. But US regulations mean that many researchers will be watching those efforts from the sidelines.

The US National Institutes of Health (NIH), which distributes the majority of federal funding for stem-cell research, prohibits research on cells taken from embryos created solely for research a category that includes the six stem-cell lines developed by Shoukhrat Mitalipov, a reproductive-biology specialist at the Oregon Health and Science University in Beaverton, and his colleagues. The team used cloning techniques to combine a donor cell with an unfertilized egg whose nucleus had been removed, creating a self-regenerating stem-cell colony that is genetically matched to the cell donor.

Mitalipovs cell lines are also off limits to researchers funded by the California Institute for Regenerative Medicine (CIRM), which was created in part to support stem-cell work that is restricted by the NIH. CIRM funds cannot be used for studies that pay women for their eggs or rely on cell lines produced using eggs from paid donors. That rules out Mitalipovs lines, because his team paid egg donors US$3,0007,000 each, says Geoffrey Lomax, senior officer to the standards working group at CIRM, which is based in San Francisco. That amount is above and beyond any out-of-pocket costs to donors, he says.

The end result, says Mitalipov, is that a dozen or so universities are struggling to negotiate material transfer agreements to receive the new cell lines without running afoul of CIRM or the NIH. Interest in the new cell lines is high, especially since the identification of errors in images and figures in Mitalipovs research paper shortly after its publication in Cell. But regulations would require laboratories to use only dedicated, privately funded equipment to study the new cells, a condition that only a fewresearchers such as George Daley, a stem-cell expert at Boston Childrens Hospital in Massachusetts will be able to meet.

That concerns Daley, who calls the NIH stem-cell policy a frustrating limitation that will preclude federal dollars being used to ask many important questions about how Mitalipovs cell lines compare with induced pluripotent stem cells (iPS), which are created by reprograming adult cells to an embryonic state. Most labs will take the path of least resistance and continue working with iPS cells unless someone shows that there is a clear and compelling reason to change course, Daley says.

Mitalipov also worries that his cell lines wont be sufficiently analyzed, which he says could hamper efforts to understand how epigenetic changes modifications to chromosomes that determine how genes are expressed affect stem cells' ability to transform into a wide array of mature cell types. We just dont have that much expertise at looking at all aspects of epigenetics, he says.

But some scientists say that the impact of US stem-cell restrictions is overestimated. Alexander Meissner, a developmental biologist at the Harvard Stem Cell Institute in Cambridge, Massachusetts, says Mitalipov's cell lines will not reveal much about how stem cells transform. That work can be done only with eggs that are easy to come by, allowing scientists to examine the reprograming process at many points. In practical terms, that means relying on eggs from mice instead of humans. Everything is over by time you derive those cell lines, he says of Mitalipovs cells. There is no signature that would tell you what has happened. Its the wrong species.

In the meantime, CIRM is re-examining the rules that govern the research its supports. The institute is not likely to alter the restrictions against funding studies that pay cell donors, but it might overturn the rules against using cell lines produced in such studies, Lomax says. The original policy was set in 2006 to address concerns that arose in the wake of fraud and ethical violations by Woo Suk Hwang, then a researcher at Seoul National University.

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Scientists Chafe at Restrictions on New Stem Cell Lines

stem cell therapy treatment for Spastic Diplegic cerebral palsy by dr alok sharma, mumbai, india
improvement seen in just 5 days after stem cell therapy treatment for Spastic Diplegic cerebral palsy by dr alok sharma, mumbai, india. Stem Cell Therapy don...

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stem cell therapy treatment for Spastic Diplegic cerebral palsy by dr alok sharma, mumbai, india - Video

14 hours ago This image shows an embryonic stem cell differentiating into a neuronal cell. Credit: Anne Rupprecht/Vetmeduni Vienna

Cells have a metabolism that can be altered according to its function. If cellular metabolism is disturbed, it can lead to disease of the entire organism. Researchers at the Vetmeduni Vienna discovered that the uncoupling proteins UCP2 and UPC4 are involved in different types of cellular metabolism. As a result, cell alterations can now be detected much earlier than was thus far possible. This research work was recently published in the PLOS ONE journal.

UCPs or uncoupling proteins are present in mitochondria, the powerhouse of each cell in the body. The functions of most of the five known UCPs remain mysterious (UCP2-UCP5), whereby only the distinct function for UCP1 has thus far been discovered. UCP1 is responsible for heat production when muscle activity is deficient such as is the case with babies and animals in hibernation. The research team at the Department of Physiology and Biophysics at the University of Veterinary Medicine in Vienna were able to provide a fundamental explanatory concept for the function of UCP2 and UPC4 for the first time. Each of these proteins are involved in different types of cell metabolism.

UCP2 in Stem Cells and Cancer Cells

In earlier studies of immune cells, lead author, Anne Rupprecht, had already shown that UCP2 could be involved in increased metabolism. Embryonic stem cells precisely exhibit such an increased metabolism, as they rapidly and continually divide, just like cancer cells. Rupprecht searched for various UCPs in embryonic stem cells of mice and in effect found UCP2. "Very high amounts of UCP2 even indicated an especially strong increase in metabolism. In other studies UCP2 had also already been detected in cancer cells", according to Rupprecht.

UCP4 in Nerve Cells

In contrast to UCP2, UCP4 is only found in nerve cells. Nerve cells have a completely different metabolism. They seldom divide, unlike stem cells and cancer cells. The research team of Prof. Elena Pohl therefore examined embryonic stem cells that differentiated to nerve cells in culture. On the basis of this model system, the researchers could show that UCP2 is still existent in the quickly reproducing stem cells, yet at the moment of differentiation are replaced by UPC4.

"In our work, we have examined the natural process of cell differentiation from stem cells to neurons. We know that metabolism changes during differentiation. The fact that we found UCP2 in one case and in the other UCP4 proves for the first time that these proteins are associated with varying types of cell metabolism", specified Elena Pohl.

The researchers, for example, found only UCP2 in neuroblastoma cells - nerve cells that have malignant changes. UCP4, the usual protein of nerve cells was not detectable. UPC4 apparently got lost in the changed nerve cells that were on their way to becoming rapidly reproductive cancer cells.

UCPs for early detection of disease

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Hot on the trail of cellular metabolism: Researchers unravel the function of cell proteins

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Newswise In a study that began in a pair of infant siblings with a rare heart defect, Johns Hopkins researchers say they have identified a key molecular switch that regulates heart cell division and normally turns the process off around the time of birth. Their research, they report, could advance efforts to turn the process back on and regenerate heart tissue damaged by heart attacks or disease.

This study offers hope that we can someday find a way to restore the ability of heart cells to divide in response to injury and to help patients recover from many kinds of cardiac dysfunction, says cardiologist Daniel P. Judge, M.D., director of the Johns Hopkins Heart and Vascular Institutes Center for Inherited Heart Diseases. Things usually heal up well in many parts of the body through cell division, except in the heart and the brain. Although other work has generated a lot of excitement about the possibility of treatment with stem cells, our research offers an entirely different direction to pursue in finding ways to repair a damaged heart.

Unlike most other cells in the body that regularly die off and regenerate, heart cells rarely divide after birth. When those cells are damaged by heart attack, infection or other means, the injury is irreparable.

Judges new findings, reported online March 4 in the journal Nature Communications, emerged from insights into a genetic mutation that appears responsible for allowing cells to continue replicating in the heart in very rare cases.

The discovery, Judge says, began with the tale of two infants, siblings born years apart but each diagnosed in their earliest weeks with heart failure. One underwent a heart transplant at three months of age; the other at five months. When pathologists examined their damaged hearts after they were removed, they were intrigued to find that the babies heart cells continued to divide a process that wasnt supposed to happen at their ages.

The researchers then hunted for genetic abnormalities that might account for the phenomenon by scanning the small percent of their entire genome responsible for coding proteins. One stood out: ALMS1, in which each of the affected children had two abnormal copies.

The Johns Hopkins researchers also contacted colleagues at The Hospital for Sick Children in Toronto, Canada, who had found the same heart cell proliferation in five of its infant patients, including two sets of siblings. Genetic analysis showed those children had mutations in the same ALMS1 gene, which appears to cause a deficiency in the Alstrm protein that impairs the ability of heart cells to stop dividing on schedule. The runaway division may be responsible for the devastating heart damage in all of the infants, Judge says.

These mutations, it turned out, were also linked to a known rare recessive disorder called Alstrm syndrome, a condition associated with obesity, diabetes, blindness, hearing loss and heart disease.

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Researchers Find Protein 'Switch' Central to Heart Cell Division

Watch the video above:Mississauga woman looking for bone marrow donor against allodds. Laura Zilke reports.

TORONTO A woman in dire need of a bone marrow transplant is trying to find a match within her underrepresented community.

Dorothy Vernon-Brown is African-Canadian and was recently diagnosed with Acute Myeloid Leukemia. Chemotherapy has helped and shes currently in remission but still needs a transplant.

You dont know if youll ever find a match, she said. Next to Caucasians, African-Canadians have the greatest need for stem cells.

Shes most likely to find a match within her own ethnic community but in Canada, only one per cent of all people registered to donate bone marrow are black.

We have patients from all ethnic communities that are currently in need of a stem cell transplant and they are relying on members of their community, whether they are living here in Canada or anywhere in the world, Mary-Lynn Pride, a spokesperson for OneMatch said.

OneMatch does have access to donor registries in over 70 countries but in Vernon-Browns native Jamaica, there isnt a registry.

Theres no studies as to why the level of African-Canadian donors is so low in Canada but she believes its cultural.

Many of us come here [and] its not part of our culture, she said. We continue with what we know.

Its not difficult to register. A simple cheek swab is all thats needed to get your name on the donor list.

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Woman looking for bone marrow donor among underrepresented ethnic group

PUBLIC RELEASE DATE:

4-Mar-2014

Contact: Jen Middleton jen.middleton@ed.ac.uk 44-131-650-6514 University of Edinburgh

Horses suffering from neurological conditions similar to those that affect humans could be helped by a breakthrough from stem cell scientists.

Researchers who are the first to create working nerve cells from horse stem cells say the advance may pave the way for cell therapies that target conditions similar to motor neurone disease.

The research could also benefit horses affected by grass sickness, a neurological condition that affects around 600 horses a year in the UK.

Little is known about the disease, which causes nerve damage throughout the body. It is untreatable and animals with the most severe form usually die or have to be put down.

The advance by the University of Edinburgh's Roslin Institute will provide a powerful tool for those studying horse diseases. It will also help scientists to test new drugs and treatments.

The researchers took skin cells from a young horse and turned them into stem cells using a technique that was originally developed for human cells. The reprogrammed cells are pluripotent, which means they can be induced to become any type of cell in the body.

The team used them to create nerve cells in the laboratory and tested whether they were functional by showing that they could transmit nerve signals in a test tube.

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Horses set to gain health benefits from stem cell advance

stem cell therapy treatment for Cerebral Palsy with Mental Retardation by dr alok sharma, mumbai
improvement seen in just 5 daysafter stem cell therapy treatment for Cerebral Palsy with Mental Retardation by dr alok sharma, mumbai, india. Stem Cell Thera...

By: Neurogen Brain and Spine Institute

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stem cell therapy treatment for Cerebral Palsy with Mental Retardation by dr alok sharma, mumbai - Video

Jesse Freeman, 71, suffered a major heart attack at home Had surgery to repair a blocked artery and to insert a stent to keep it open He was then asked to take part in a new study into the use of stem cells These are 'master cells' which can turn into almost any other type of cell in the body, replacing damaged cells He had bone marrow removed from his hip and infused into his heart It is hoped this will regenerate to help heal his damaged heart

By Emma Innes

PUBLISHED: 08:36 EST, 3 March 2014 | UPDATED: 08:52 EST, 3 March 2014

A British man has become the second patient in a Europe to have pioneering stem cell treatment in a bid to prolong his life.

Jesse Freeman, 71, was invited to take part in the landmark trial after suffering a major heart attack at home.

Surgeons repaired a blocked artery and inserted a stent to keep it open after he was rushed to hospital.

Jesse Freeman (pictured with his wife, Christine) has become the second person in Europe to have pioneering stem cell treatment after a heart attack. It is hoped the procedure will cause his damaged heart muscle to regenerate and that it could eventually become common practice in the treatment of heart attack patients

But while recovering in hospital, he was asked to take part in the major new study to see if heart attack patients can benefit from being treated with their own stem cells.

These are 'master cells' which can turn into almost any other type of cell in the body, replacing damaged cells.

Doctors at the London Chest Hospital, in Bethnal Green, removed bone marrow from Mr Freeman, a grandfather, without general anaesthetic and the cells were then infused into his heart.

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Is this the heart attack treatment of the future? British grandfather has stem cells taken from his hip and injected ...

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Researchers in London, UK, are investigating the effectiveness of stem cell therapies for facial reconstruction.

A joint team, from London's Great Ormond Street Hospital for Children and University College London's Institute of Child Health, has published the findings of their research in the journal Nanomedicine.

This follows the recent news that another UK-based team, of The London Chest Hospital, has begun the largest ever trial of adult stem cells in heart attack patients.

Great Ormond Street has a proven track record in facial reconstruction, particularly with regard to treating children with a missing or malformed ear - a condition called microtia. This kind of reconstructive surgery involves taking cartilage from the patient's ribs to craft a "scaffold" for an ear, which is then implanted beneath the skin.

Despite successes with this method, the researchers thought the treatment may be improved by bringing stem cells into the process.

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Reconstructing faces using human stem cells from fat