Stem Cell Clinic

Alzheimer's research team employs stem cells to understand disease processes and study new treatment

By Stem Cell Treatment

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

Patient-Specific Human Embryonic Stem Cells Created by Cloning

By Stem Cell Medicine

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

New OHSU center aims to speed cures for Parkinson’s …

By Stem Cell Medical Center

Enlarge Photo

OHSU's Dr. Shoukhrat Mitalipov will lead the hospital's new Center for Embryonic Stem Cell and Gene Therapy.

Oregon Health & Science University has launched a new Center for Embryonic Cell and Gene Therapy.

Led by renowned researcher Dr. Shoukhrat Mitalipov, a senior scientist at OHSU's Oregon National Primate Research Center, the center could help accelerate cures and treatments for Parkinson's disease, multiple sclerosis and other conditions caused by diseased or injured cells.

"Our continuing work and discoveries can be revolutionary in how we cure and treat many diseases and injuries," said Mitalipov in a statement. "This new center will allow us to put together a comprehensive program where we can share our expertise, answer new questions and train the scientists needed to move this important work forward."

Mitalipov and his team have succeeded in preventing transmission of genetic defects in mitochondrial DNA in the cells of monkeys, in 2009, and in human cells in 2012. Thousands of babies are born every year in the U.S. with mutated mitochondrial DNA, which can cause brain damage, muscle weakness, cardiac disease and damage to other organs. Most children with mitochondrial disease don't live past their teenage years.

Mitalipov just returned from a two-day Food and Drug Administration hearing in Maryland that reviewed his gene therapy research for consideration of human clinical trials.

Mitalipov and his team are also global leaders in embryonic stem cell research. Last year, the journal Cell published a Mitalipov paper that detailed how his team had reprogrammed human skin cells to become embryonic stem cells capable of transforming into any cell type in the body.

Stem cell therapies may eventually allow damaged cells to be replaced and could be key contributors to treating Parkinson's disease, cardiac disease and spinal cord injuries, among other conditions. Mitalipov's procedure is among a very few alternatives to the controversial use of stem cells derived from fertilized human embryos. His lab is the only one in the world currently capable of producing these embryonic human stem cells.

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New OHSU center aims to speed cures for Parkinson's ...

Scientists Chafe at Restrictions on New Stem Cell Lines

By Uncategorized

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

OHSU Photos

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 – Video

By Uncategorized


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...

By: Neurogen Brain and Spine Institute

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

Chronically sprained ankle – three months after stem cell treatment by Dr Harry Adelson – Video

By Stem Cell Treatment


Chronically sprained ankle - three months after stem cell treatment by Dr Harry Adelson
Stacy discusses her results from her stem cell treatment by Dr Harry Adelson for her chronically sprained ankle http://www.docereclinincs.com.

By: Harry Adelson, N.D.

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Chronically sprained ankle - three months after stem cell treatment by Dr Harry Adelson - Video

Stem cell treatment, other breakthroughs giving pets longer, healthier lives

By Stem Cell Treatment

(WMC-TV) - More than 60 percent of American households include at least one pet, and for many of us they are more like family than a four-legged friend.

Eight-year-old Sadie suffers from debilitating arthritis. To owners Greg and Marsha James, she is a miracle dog.

"She's my little girl, she's my baby," said owner Marsha. "I didn't know if we could do anything and what we could do, I thought we were gonna lose her."

Last year she could not even walk, but a scientific breakthrough using her own stem cells put the pep back in her step.

"Stem cell is used to treat chronic arthritic conditions," said Dr. Kathy Mitchener, DVM at Angel Care Center for Pets.

Dr. Kathy Mitchener removed a few ounces of fat from Sadie's tummy; a lab extracted the stem cells, which were then re-injected into her trouble spots.

"If there's joint destruction, if there's changes in metabolism then they change themselves and multiply to help address those issues," said Mitchener.

Stem cell treatment proves to be just one of many medical miracles at the Angel Care Cancer Center for Pets in Bartlett.

Take Rylee for example. The 2-year-old golden retriever has an unusual type of lymphoma.

"Riley was very young, and that's very , very frightening to have such a devastating disease," said Mitchener.

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Stem cell treatment, other breakthroughs giving pets longer, healthier lives

Painkillers Could Prove Helpful in Stem-Cell Transplants

By Stem Cell Treatment

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

First Road Map of Human Sex-Cell Development

By Stem Cell Treatment

A new study marks a step toward stem cell treatment of infertility

Clouds Hill Imaging Ltd./Corbis

The causes of infertility, which affects around 10% of couples, are often unknown, but may in some cases result from the body's inability to produce viable gametes also known as sperm and egg cells. The first study of the development of such 'germ cells' from humans could help scientists to learn how to create them in the laboratory instead.

Even though the reproductive age for humans is around 1545 years old, the precursor cells that go on to produce human eggs or sperm are formed much earlier, when the fertilized egg grows into a tiny ball of cells in the mothers womb. This ball of cells contains pluripotent stem cells blank slates that can be programed into any type of cell in the body and researchers are hoping to use these stem cells to treat various conditions, including infertility.

But little is known about the early developmental stages of human gametes owing to the sensitivity of working with human tissue and most work in this area has been conducted using mice. In a Nature Cell Biology paper today, researchers from the University of California, Los Angeles, trace the development of early germ cells in human fetuses of between 6 to 20 weeks and analyzed when genes were turned on or off.

The DNA within these early germ cells carries 'epigenetic modifications' structural changes that do not affect the DNA sequence itself but do affect the way that genes are expressed. These changes may have accumulated during the parents lives, and need to be erased during the fetal stage. The study found two major events that wipe out, or reprogram, epigenetic modifications. Most of this reprograming happened before 6 weeks, but the authors found a second event that completes the reprograming after 6 weeks.

This is an important and fundamental paper for understanding human germ-line cells and finding the basic information about human germ-cell biology, says reproductive biologist Evelyn Telfer of the University of Edinburgh, UK. The researchers are clearly working in an uncharted area.

The Los Angeles team worked with anonymized samples from aborted fetuses (after consent) from the University of Washington's Birth Defects Research Laboratory in Seattle.

The researchers also observed that 6-week-old germ cells created in the lab do not match a 6-week-old human germ cell, suggesting that there is a blockage in the development of lab cells that scientists are failing to understand.

Next, we need to look at what is missing to coax immature germ cells to become eggs or sperm in the lab. If we have no road map to follow, then we are just guessing. Now we have a snapshot of what these cells should look like, we can start to try and mimic them, says study co-author Amander Clark.

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First Road Map of Human Sex-Cell Development

Stem cell technology to cure spinal cordv injuries introduced in KSA

By Stem Cell Treatment

The Sultan bin Abdulaziz Humanitarian City (SAHC) announced Tuesday its intention to take stem cell transplantation to new heights by using the method to cure spinal cord injuries. The announcement was made by Prince Khaled bin Sultan, chairman of the Sultan bin Abdulaziz Al-Saud Foundation (SAAF), during the international spinal cord injury conference 2014, which kicked off at the SAHC headquarters on Tuesday. The theme of the conference, which ends on Thursday, is Toward a Better Quality of Life. The conference, first introduced in Australia and New Zealand, is being held for the first time in the Middle East. The technology, in collaboration with the US-based University of Miami, will revolutionize the scope of paralysis surgery in the Kingdom, making it a leader in the field. An accord on collaboration between the SAHC and the Miami Project to Cure Paralysis (MPCP), the first center in the US to receive approval from the supervisory board of the Food and Drug Administration for stem cell therapy, was also signed. Prince Khaled said that the transfer of this technology comes amid efforts to help families cope with the life-changing effects of spinal cord injuries. Prince Khaled said many people between the ages of 16 and 22 suffer such debilitating injuries. The MPCP works on several research and rehabilitation programs in the field of spinal cord and traumatic brain injury, he said. The transfer of this technology to the SAHC will make Saudi Arabia one of the first countries in the region to benefit from the revolutionary treatment of spinal cord injury through stem cell research. SAHC Executive President Abdullah Zarah said the conference would address the latest findings of modern science in the field of spinal cord injury and stem cell transplantation. Around 1,500 Saudis are afflicted with spinal cord injuries every year due to accidents. Rizman Hamid, a senior neurology lecturer at University College London, told Arab News that being afflicted with this type of injury is a lifelong condition. Such critical ailments require follow-up, with radiological investigation to optimize bladder function. Patients should undergo regular investigation as a means of detecting potential problems in the bladder, which can lead to kidney damage, he said. He added that another major problem resulting from spinal cord injuries, especially among women, is urinary incontinence, which has severe and adverse effects on patients. This condition can be cured through a procedure known as the transobtruator tape. This is a minimally invasive procedure that has good long-term results, he said. Firas Sirhan, director of the Center of Excellence for Telehealth and Assisted Living (CETAL) at Buckinghamshire New University in Middlesex, England, said that the use of technology and health care practice is becoming more visible in the treatment and management of spinal cord injuries. Telehealth represents an entirely new way of managing injury that does not easily fit within existing health care frameworks, he said. The use of the telehealth model has contributed to empowering patients to become more involved in the self-management of their condition. Telehealth could be an effective tool that contributes to allowing health care professionals, as well as patients, to recognize and identify any changes in medical conditions. He added that the center can assist in developing packages that combine tested clinical service models with assessed technology to present workable telehealth services based on specific needs.

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Stem cell technology to cure spinal cordv injuries introduced in KSA

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