Posted: March 8, 2014 at 7:45 am
Stem Cell Therapies for Leukemia: Marching Toward the Clinic
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By: California Institute for Regenerative Medicine
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Stem Cell Therapies for Leukemia: Marching Toward the Clinic - Video
Posted: March 8, 2014 at 2:46 am
By Marcus Johnson
Stem cell researchers from Harvard have been able to turn patients skin cells into neurons that can be affected by early-onset Alzheimers. Experts believe that this will make it easier to gather the results of cells affected by the disease. It is also believed that the research will make the development of new treatments a faster process.
The research was published in the Human Molecular Genetics journal and headed by Tracy Young-Pearse. The data showed that peopl suffering from Alzheimers had cell mutations t similar to mutations occurring in mice. We see this mild increase in A42 in cells from patients with Alzheimer's disease, which seems to be enough to trigger disease processes, said Young-Pearse. We also see increases of a smaller species of amyloid-beta called A38, which was unexpected as it should not be very aggregation prone. We don't fully understand what it means, but it may combine with other forms of amyloid-beta to stimulate plaque formation.
The researchers hope that their work can lead to new drugs that are more effective against the disease. Alzheimers drugs have had a high rate of failure during clinical trials because much of the drug development was based on non-human models. Young-Pearse hopes that their research can make it easier to treat the disease and develop new drugs. Because of the Harvard Stem Cell Institute, we were able to work with other researchers to make patient cells into any type of neuron," said Young-Pearse. "The environment provides a really nice system for testing many kinds of hypotheses.
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Stem Cells Driving Alzheimer's Research
Posted: March 7, 2014 at 3:48 am
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
Posted: March 7, 2014 at 3:48 am
PUBLIC RELEASE DATE:
6-Mar-2014
Contact: Jessica Maki jmaki3@partners.org 617-525-6373 Brigham and Women's Hospital
Boston, MA A team of Alzheimer's disease (AD) researchers at Brigham and Women's Hospital (BWH) has been able to study the underlying causes of AD and develop assays to test newer approaches to treatment by using stem cells derived from related family members with a genetic predisposition to (AD).
"In the past, research of human cells impacted by AD has been largely limited to postmortem tissue samples from patients who have already succumbed to the disease," said Dr. Tracy L. Young-Pearse, corresponding author of the study recently published in Human Molecular Genetics and an investigator in the Center for Neurologic Diseases at BWH. "In this study, we were able to generate stem cells from skin biopsies of living family members who carry a mutation associated with early-onset AD. We guided these stem cells to become brain cells, where we could then investigate mechanisms of the disease process and test the effects of newer antibody treatments for AD."
The skin biopsies for the study were provided by a 57-year-old father with AD and his 33 year-old- daughter, who is currently asymptomatic for AD. Both harbor the "London" familial AD Amyloid Precursor Protein (APP) mutation, V7171. More than 200 different mutations are associated with familial AD. Depending on the mutation, carriers can begin exhibiting symptoms as early as their 30s and 40s. APPV7171 was the first mutation linked to familial AD and is the most common APP mutation.
The BWH researchers submitted the skin biopsies to the Harvard Stem Cell Institute, where the cells were converted into induced pluripotent stem cells (or iPSCs). Dr. Young-Pearse's lab then directed the stem cells derived from these samples into neurons specifically related to a particular region of the brain which is responsible for memory and cognitive function. The scientists studying these neurons made several important discoveries. First, they showed that the APPV7171 mutation alters APP subcellular location, amyloid-beta protein generation, and then alters Tau protein expression and phosphorylation which impacts the Tau protein's function and activity. Next, the researchers tested multiple amyloid-beta antibodies on the affected neurons. Here, they demonstrated that the secondary increase in Tau can be rescued by treatment with the amyloid -protein antibodies, providing direct evidence linking disease-relevant changes in amyloid-beta to aberrant Tau metabolism in living cells obtained directly from an AD patient.
While AD is characterized by the presence of amyloid-beta protein plaques and Tau protein tangles, observing living cell behavior and understanding the mechanisms and relationship between these abnormal protein deposits and tangles has been challenging. Experimental treatments for AD are using antibodies to try to neutralize the toxic effects of amyloid-beta, because they can bind to and clear the amyoid-beta peptide from the brain.
This study is the first of its kind to examine the effects of antibody therapy on human neurons derived directly from patients with familial AD.
"Amyloid-beta immunotherapy is a promising therapeutic option in AD, if delivered early in the disease process," said Dr. Young-Pearse. "Our study suggests that this stem cell model from actual patients may be useful in testing and comparing amyloid-beta antibodies, as well as other emerging therapeutic strategies in treating AD."
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Alzheimer's research team employs stem cells to understand disease processes and study new treatment
Posted: March 7, 2014 at 3:48 am
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
Posted: March 7, 2014 at 3:48 am
In an effort to bring clarity to one of the most controversial and confusing scientific findings in recent memory, three Japanese scientists have released a detailed protocol explaining step by step how to create stem cells with a simple acid bath. A leading stem cell scientist at Boston Childrens Hospital is working directly with the scientist who led the work to try and repeat the technique.
The surprising report in January by Boston and Japanese scientists that stem cells, with the ability to develop into any cell in the body, could be created with the seemingly straightforward technique sparked a raging and very public debate in the scientific community.
Within a month, a problem with images in one of the papers was revealed, which the scientists have said will be corrected. Other possible problems have been pointed out on online forums. An investigation by the Japanese scientists institution has been ongoing, spurred by questions raised by outside scientists.
What can be easy to forget is that it is not unusual for a new technique that upsets conventional knowledge to be carefully and critically vetted. That process is appropriate and part of how science works; its just usually hidden from public view. Only rarely are discoveries so unexpected and high-profile that they trigger this level of public skepticism. The ultimate test of the stem cell-creation technique, as with any other scientific discovery, will be whether it can be repeated by other scientists.
The doubts have gushed out over the last month. Laboratories across the world have been trying to replicate the result, and people have shared reports of initial failures, although many of those were using different types of cells than those the authors reported using in their paper.
It is also is not uncommon for an experiment to not work when it is first attempted, so reports of a failure dont mean the technique is wrong or doesnt work. The new protocol will provide scientists a careful recipe to followallowing them to rule out that differences in their technique might be causing them to fail.
In Boston, there are several scientists who are working to repeat the technique. I asked Dr. George Q. Daley, a stem cell scientist at Childrens Hospital and the Harvard Stem Cell Institute, what his experience has been so far.
Daley said he is working directly with Dr. Charles Vacanti, the anesthesiologist at Brigham and Womens Hospital who was the senior author on the paper describing the technique. Although many have been quick to air their doubts about whether the method is just too good to be true, Daley said he would like to feed the evidence base and not the rumor mill. Vacanti, he said, has been very helpful and cooperative.
If the technique is robust and highly reproducible it will be replicated quickly. If there are subtleties and nuances of the technique, then it will take longer. Only time will tell, and this is how science works, Daley wrote. If there is some fatal flaw in the technique, then it will be revealed in time. I am concerned about the rush to use blogging and social media to report early experience with a complex biological experiment. Most scientific experiments take time and many replications to work confidently, and early reporting may reflect a negative bias.
In an e-mail, Vacanti said that the reason he is not a coauthor on the protocol that has been posted by the Japanese RIKEN Institute where many of his coauthors work is because he was not asked to take part.
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Efforts to repeat controversial stem cell technique intensify
Posted: March 7, 2014 at 3:48 am
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
Posted: March 7, 2014 at 3:44 am
The approach involves using enzymes to destroy a gene in the immune cells of people with HIV, thereby increasing resistance to the virus
Scanning electron micrograph of a human T cell from the immune system of a healthy donor. Credit:NIAID/NIH - Wikimedia Commons
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. The findings were published March 5 in The New England Journal of Medicine.
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 thatBrown gained the ability to control his HIV infectionafter they treated him with donor bone-marrow stem cells that carried a mutation in a gene calledCCR5. Most HIV strains use a protein encoded byCCR5as 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 isnot 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 beneficialCCR5 mutation in a persons own cells, using targeted gene editing.
Personalized medicine 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 theCCR5gene 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 functionalCCR5gene, 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?
Long-term action 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 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 Technique Shown to Work as HIV Treatment
Posted: March 7, 2014 at 3:40 am
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...
By: Cells Center China
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21.Spinal Cord Injury(T5-6) Treated by Stem Cell Therapy(Before) - Video
Posted: March 7, 2014 at 3:40 am
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.
