Category Archives: Stem Cell Videos

David Rowitch, MD, PhD, professor and chief of neonatology, in the NICU.

A Phase I clinical trial led by investigators from the University of California, San Francisco (UCSF) and sponsored by Stem Cells Inc., showed that neural stem cells successfully engrafted into the brains of patients and appear to have produced myelin.

The study, published in Wednesday's issue of Science Translational Medicine, also demonstrated that the neural stem cells were safe in the patients brains one year post transplant.

The results of the investigation, designed to test safety and preliminary efficacy, are encouraging, said principal investigator David H. Rowitch, MD, PhD, a professor of pediatrics and neurological surgery at UCSF, chief of neonatology at UCSF Benioff Childrens Hospital and a Howard Hughes Medical Institute Investigator.

Nalin Gupta, MD, PhD

For the first time, we have evidence that transplanted neural stem cells are able to produce new myelin in patients with a severe myelination disease, said Nalin Gupta, MD, PhD, associate professor of neurological surgery and pediatrics and chief of pediatric neurological surgery at UCSF Benioff Children's Hospital, and co-principal investigator of the PMD clinical trial.

We also saw modestgains in neurological function, and while these cant necessarily be attributed to the intervention because this was an uncontrolled trial with a small number of patients,the findings represent an important first step that strongly supports further testing of this approach as a means to treat the fundamental pathology in the brain of these patients.

The study, one of the first neural stem cell trials ever conducted in the United States, is emblematic of UCSFs pioneering role in the stem cell field. In 1981, Gail Martin, PhD, professor of anatomy, co-discovered embryonic stem cells in mice. In 2001, Roger Pedersen, PhD, professor emeritus of obstetrics, gynecology and reproductive sciences, derived two of the first human embryonic stem cell lines. On Monday, Shinya Yamanaka, MD, PhD, of the UCSF-affiliated Gladstone Institutes and Kyoto University, received the Nobel Prize in Physiology or Medicine for his discovery that adult cells can be reprogrammed to behave like embryonic stem cells.

In the trial, human neural stem cells developed by Stem Cells, Inc., of Newark, California, were injected directly into the brains of four young children with an early-onset, fatal form of a condition known as Pelizaeus-Merzbacher disease (PMD).

This image illustrates direct injection of human neural stem cells into the brain's white matter, which is composed of bundles of nerve axons. There is lack of myelin, an insulating coating, in the severe pediatric condition Pelizaeus-Merzbacher disease (PMD). Over time, some stem cells become myelinating oligodendrocytes as reported in the papers from Uchida et al. and Gupta et al. Image by Kenneth Probst.

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Transplanted Neural Stem Cells Produced Myelin, UCSF Study Shows

Public release date: 10-Oct-2012 [ | E-mail | Share ]

Contact: Jennifer O'Brien jennifer.obrien@ucsf.edu 415-502-6397 University of California - San Francisco

A Phase I clinical trial led by investigators from the University of California, San Francisco and sponsored by Stem Cells Inc., showed that neural stem cells successfully engrafted into the brains of patients and appear to have produced myelin.

The study, published in the Oct. 10, 2012 issue of Science Translational Medicine, also demonstrated that the neural stem cells were safe in the patients' brains one year post transplant.

The results of the investigation, designed to test safety and preliminary efficacy, are encouraging, said principal investigator David H. Rowitch, MD, PhD, a professor of pediatrics and neurological surgery at UCSF, chief of neonatology at UCSF Benioff Children's Hospital and a Howard Hughes Medical Institute Investigator.

"For the first time, we have evidence that transplanted neural stem cells are able to produce new myelin in patients with a severe myelination disease," said Nalin Gupta, MD, PhD, associate professor of neurological surgery and pediatrics and chief of pediatric neurological surgery at UCSF Benioff Children's Hospital, and co-principal investigator of the PMD clinical trial.

"We also saw modest gains in neurological function, and while these can't necessarily be attributed to the intervention because this was an uncontrolled trial with a small number of patients, the findings represent an important first step that strongly supports further testing of this approach as a means to treat the fundamental pathology in the brain of these patients."

In the trial, human neural stem cells developed by StemCells, Inc., of Newark, California, were injected directly into the brains of four young children with an early-onset, fatal form of a condition known as Pelizaeus-Merzbacher disease (PMD).

In PMD, an inherited genetic defect prevents brain cells called oligodendrocytes from making myelin, a fatty material that insulates white matter which serves as a conduit for nervous impulses throughout the brain. Without myelin sheathing, white matter tracts short-circuit like bare electrical wires and are unable to correctly propagate nerve signals, resulting in neurological dysfunction and neurodegeneration. Patients with early-onset PMD cannot walk or talk, often have trouble breathing and undergo progressive neurological deterioration leading to death between ages 10 and 15.The disease usually occurs in males.

Multiple sclerosis and certain forms of cerebral palsy also involve damage to oligodendrocytes and subsequent demyelination.

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UCSF study shows evidence that transplanted neural stem cells produced myelin

NEWARK, Calif., Oct. 10, 2012 (GLOBE NEWSWIRE) -- StemCells, Inc. (STEM) today announced that two papers reporting clinical and preclinical data demonstrating the therapeutic potential of the Company's proprietary HuCNS-SC(R) cells (purified human neural stem cells) for a range of myelination disorders were published in the Oct. 10 edition of Science Translational Medicine, the peer review journal of the American Association for the Advancement of Science (http://stm.sciencemag.org/).

The paper by Gupta, et al. describes the encouraging results of the Company's Phase I clinical trial in Pelizaeus-Merzbacher disease (PMD), a genetic myelination disorder that afflicts children. In the trial, which was completed in February 2012, four patients were transplanted with the Company's HuCNS-SC cells and all showed preliminary evidence of progressive and durable donor cell-derived myelination. Three of the four patients showed modest gains in their neurological function, which suggests a departure from the natural history of the disease; the fourth patient remained stable. Although clinical benefit cannot be confirmed in a trial without control patients, the small but measureable gains in function at one year may represent signals of a clinical effect to be further investigated in a controlled trial with more patients.

The second of the two papers, by Uchida, et al., summarizes extensive preclinical research which demonstrated that transplantation of the Company's neural stem cells in an animal model of severe myelin deficiency results in new myelin which enhanced the conductivity of nerve impulses. Myelin is the substance that insulates nerve axons, and without sufficient myelination, nerve impulses are not properly transmitted and neurological function is impaired. This preclinical data provided the rationale for the PMD clinical trial and supports the Company's cell therapy approach to other myelination disorders, such as transverse myelitis, certain forms of cerebral palsy, and multiple sclerosis.

"For the first time, we have evidence that transplanted neural stem cells are able to produce new myelin in patients with a severe myelination disease," Nalin Gupta, MD, PhD, associate professor of neurological surgery and pediatrics and chief of pediatric neurological surgery at UCSF Benioff Children's Hospital, and co-principal investigator of the PMD clinical trial. "We also saw modest gains in neurological function, and while these can't necessarily be attributed to the intervention because this was an uncontrolled trial with a small number of patients, it is an important first step which provides hope that HuCNS-SC transplantation may be able to address the fundamental pathology in the brain of PMD patients."

Patients with PMD have a defective gene which leads to insufficient myelin in the brain, which leads to a progressive loss of neurological function and death. In the clinical trial, four patients with connatal PMD, the most severe form of the disease, were enrolled and transplanted with HuCNS-SC cells. The patients were followed for twelve months after transplantation, during which time they underwent intensive neurological assessments and magnetic resonance (MR) imaging at regular intervals. The findings from the trial indicate a favorable safety profile for the HuCNS-SC cells and the transplantation procedure. Analysis of the MR imaging data showed changes consistent with increased myelination in the region of the transplantation, and which progressed over time and persisted after the withdrawal of immunosuppression at nine months. The results support the conclusion of durable cell engraftment and donor-derived myelin in the transplanted patients' brains. The development of new myelin signals is unprecedented in patients with connatal PMD. In addition, clinical assessment revealed small but measureable gains in motor and/or cognitive function in three of the four patients; the fourth patient remained clinically stable. While clinical benefit cannot be confirmed without a controlled study, these clinical outcomes suggest the HuCNS-SC cells may be having a beneficial effect on the patients.

The second paper, whose lead author is Nobuko Uchida, Vice President of Stem Cell Biology at StemCells, Inc., describes research which shows that when HuCNS-SC cells were transplanted into the shiverer mouse, a common model of severe central nervous system (CNS) dysmyelination, the cells formed new, functional myelin in the mice. Sophisticated analytical techniques were used to confirm that changes measured by MR images were in fact derived from new human myelin generated by the transplanted HuCNS-SC cells. MR imaging is routinely used in the diagnosis and clinical characterization of demyelinating diseases such as multiple sclerosis, and these results supported the use of similar techniques to detect and evaluate the degree of myelination in the Phase I PMD trial. Moreover, the new myelin was shown to be functional as conductivity of nerve impulses in the mice was enhanced.

"Demonstration of functional myelin formation in animals showing disease symptoms is significant and opens up the potential to treat patients with a range of severe myelin disorders," said Stephen A. Back, MD, PhD, professor of pediatrics and neurology at Oregon Health & Science University Doernbecher Children's Hospital, and senior author of the preclinical paper.

Stephen Huhn, MD, FACS, FAAP, Vice President and Head of the CNS Program at StemCells, Inc., added, "Having these two papers published concurrently illustrates the direct pathway of how we are translating groundbreaking scientific research to the clinical setting. The data in these papers make a powerful statement about the potential of our HuCNS-SC cells to address not only PMD, but a wide spectrum of myelination disorders. We are actively moving forward with our plans to conduct a controlled Phase II clinical study in PMD and evaluating our next steps with respect to other myelination disorders."

Conference Call

StemCells, Inc. will host a live webcast, today, October 10, at 4:30 p.m. Eastern Time (1:30 p.m. Pacific Time) to discuss the data reported in these papers. Interested parties are invited to view the webcast over the Internet via the link at http://www.stemcellsinc.com/News-Events/Events.htm. An archived version of the webcast will be available for replay on the Company's website approximately two hours following the conclusion of the live event and will be available for a period of 30 days.

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StemCells, Inc. Announces Simultaneous Publication of Preclinical and Clinical Results of Its Neural Stem Cells for ...

ScienceDaily (Oct. 10, 2012) Physician-scientists at Oregon Health & Science University Doernbecher Children's Hospital have demonstrated for the first time that banked human neural stem cells -- HuCNS-SCs, a proprietary product of StemCells Inc. -- can survive and make functional myelin in mice with severe symptoms of myelin loss. Myelin is the critical fatty insulation, or sheath, surrounding new nerve fibers and is essential for normal brain function.

This is a very important finding in terms of advancing stem cell therapy to patients, the investigators report, because in most cases, patients are not diagnosed with a myelin disease until they begin to show symptoms. The research is published online in the journal Science Translational Medicine.

Myelin disorders are a common, extremely disabling, often fatal type of brain disease found in children and adults. They include cerebral palsy in children born prematurely as well as multiple sclerosis, among others.

Using advanced MRI technology, researchers at OHSU Doernbecher Children's Hospital also recently recognized the importance of healthy brain white matter at all stages of life and showed that a major part of memory decline in aging occurs due to widespread changes in the white matter, which results in damaged myelin and progressive senility (Annals of Neurology, September 2011).

In this breakthrough study, Stephen A. Back, M.D., Ph.D., senior author and clinician-scientist in the Pap Family Pediatric Research Institute at OHSU Doernbecher Children's Hospital, used a transgenic mouse model (Shiverer-immunodeficient) that develops progressive neurological deterioration because it is unable to make a key protein required to make normal myelin. Although this mouse has been widely investigated, prior to this study, true human brain-derived stem cells had not been tested for their potential to make new myelin in animals that were already deteriorating neurologically.

"Typically, newborn mice have been studied by other investigators because stem cells survive very well in the newborn brain. We, in fact, found that the stem cells preferentially matured into myelin-forming cells as opposed to other types of brain cells in both newborn mice and older mice. The brain-derived stem cells appeared to be picking up on cues in the white matter that instructed the cells to become myelin-forming cells," explained Back.

Although Back, in collaboration with investigators at StemCells Inc., had achieved success implanting stem cells in presymptomatic newborn animals, it was unclear whether the cells would survive after transplant into older animals that were already declining in health. Back and his colleagues put these cells to the test by transplanting them in animals that were declining neurologically and found that the stem cells were able to effectively survive and make functional myelin.

The study also is important because the research team was able to confirm by MRI that new myelin had been made by the stem cells within weeks after the transplant. Until now, it was unclear whether stem cell-derived myelin could be detected without major modifications to the stem cells, such as filling them with special dyes or iron particles that can be detected by the MRI.

These studies were particularly challenging, Back explained, because the mice were too sick to survive in the MRI scanner. Fortunately, OHSU is home to a leading national center for ultra-high field MRI scanners that were used to detect the myelin made by normal, unmodified stem cells.

"This is an important advance because it provides proof of principle that MRI can be used to track the transplants as myelin is being made. We actually confirmed that the MRI signal in the white matter was coming from human myelin made by the stem cells," Back said.

Excerpt from:
Human neural stem cells study offers new hope for children with fatal brain diseases

BY LAURA OLENIACZ

loleniacz@heraldsun.com; 919-419-6636

DURHAM Stem cells from umbilical cord blood saved at 14-month-old Jase Howells birth are now being used in research to see if the cells can help his brain heal.

The research is looking into the use of the stem cells to treat brain damage from hydrocephalus, a condition characterized by the buildup of fluid in the skull.

His family traveled from Texas so he could receive an infusion on Tuesday at the Duke Childrens Hospital & Health Center of cord blood that was saved at his birth.

Mommys so proud of you, said LeaAnn Howell, to Jase, as he lay on a hospital bed, surrounded by medical personnel and family.

He periodically lifted his leg up and down to the beat of The Wheels on the Bus and other songs played by music therapist Tray Batson during the procedure.

Like I said, we were going to do anything humanly possible that we can do, Howell said in an interview prior to the procedure. Its a tough thing to fly, but once we (get here), I think the results are worth the wait, I guess.

The research into the use of cord blood stem cells to treat brain injury from hydrocephalus is being led by Dr. Joanne Kurtzberg, chief of the Division of Pediatric Blood and Marrow Transplantation at Duke.

The research is being done under a U.S. Food and Drug Administration Investigational New Drug application, Kurtzberg said.

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Duke med school gets FDA approval for stem cell product

Four boys with a rare and often fatal brain disease were implanted with stem cells that began fixing damage that impeded their ability to walk, talk and eat, a trial found.

The findings, published today in the journal Science Translational Medicine, are from the first stage of human tests funded by StemCells Inc. (STEM), a Newark, California-based company.

The children have a genetic disorder called Pelizaeus- Merzbacher, in which the brain cant make myelin, the fatty insulation for nerve cells that helps conduct brain signals. The children all had evidence of myelin growth a year later. The increased abilities shown by three of the boys in the University of California San Francisco study may bode well for other diseases caused by a lack of myelin insulation, including multiple sclerosis and cerebral palsy, the authors wrote.

Those were severely impaired children, said Stephen Back, a professor of pediatrics and neurology at Portlands Oregon Health & Science University, in a telephone interview. The fact that they showed any neurological improvement is very encouraging.

Back did work in mice that preceded todays work in humans, which he wasnt directly involved in. His study, published simultaneously, showed that the animals with no myelin at all grew some after being implanted with human stem cells.

Pelizaeus-Merzbacher disease causes the degeneration of the nervous system, and there is no cure or standard treatment. People with the illness experience a loss of coordination, thinking and motor abilities. Its one of several disorders linked to genes that control myelin production.

The incidence of the disease is 1 in 200,000 to 500,000 people, according to todays study of the boys.

The boys were between the ages of 1 and 6. They were given purified neural stem cells from a fetal brain, which was then grown in culture. The stem cells were inserted into the frontal lobe, using brain imaging as a guide. The boys brains were scanned 24 to 48 hours after surgery to assess safety.

The children were on drugs to suppress their immune systems and prevent their bodies from rejecting the stem cells for nine months. Side effects included rashes, diarrhea and fever. One boy had fluid collect under his scalp, which later vanished on its own. A second subject had some bleeding in the brain after the surgery, which was without clinical consequence, according to the paper.

One of the boys developed the ability to take steps with assistance and began to speak single words. Another started eating solid food on his own. A third began to walk without the assistance of a walker and began eating on his own.

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Brain Stem-Cell Implants Help Children With Rare Illness

A Japanese and a British scientist were awarded the 2012 Nobel Prize in physiology or medicine Monday for their groundbreaking work in turning adult cells into immature ones that might be tweaked further to treat a wide spectrum of diseases. Such research is being aggressively pursued at scientific institutions across San Diego County.

Shinya Yamanaka of Japan and John Gurdon of Great Britain showed that it is possible to alter adult cells to the point where they are very similar to human embryonic stem cells. But the process does not involved the destruction of embryos.

In essence, scientists can now take cells from, say, a person's skin and turn back the clock, making the cell essentially act as though it were new.

The Nobel Assembly at the Karolinska Institute issued a statement today saying, "These groundbreaking discoveries have completely changed our view of the development and cellular specialisation. We now understand that the mature cell does not have to be confined forever to its specialised state. Textbooks have been rewritten and new research fields have been established. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy.

"The discoveries of Gurdon and Yamanaka have shown that specialised cells can turn back the developmental clock under certain circumstances. Although their genome undergoes modifications during development, these modifications are not irreversible. We have obtained a new view of the development of cells and organisms.

"Research during recent years has shown that iPS cells can give rise to all the different cell types of the body. These discoveries have also provided new tools for scientists around the world and led to remarkable progress in many areas of medicine. iPS cells can also be prepared from human cells.

"For instance, skin cells can be obtained from patients with various diseases, reprogrammed, and examined in the laboratory to determine how they differ from cells of healthy individuals. Such cells constitute invaluable tools for understanding disease mechanisms and so provide new opportunities to develop medical therapies."

Gurdon -- who was working in his lab today when he learned that he'd won a Nobel -- made the initial breakthrough about 50 years ago, and Yamanaka built on that work, accelerating the process through genetic engineering.

The Sanford-Burnham Medical Research Institute was created in La Jolla, in part, to probe exactly this area of research.

Will La Jolla scientists win this year's Nobel Prizes?

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Nobel Prize awarded for work on stem cells

NEW YORK -- Two scientists from different generations won the Nobel Prize in medicine Monday for the groundbreaking discovery that cells in the body can be reprogrammed into completely different kinds -- work that reflects the mechanism behind cloning and offers an alternative to using embryonic stem cells.

The work of British researcher John Gurdon and Japanese scientist Shinya Yamanaka -- who was born the year Gurdon made his discovery -- holds hope for treating diseases such as Parkinson's and diabetes by growing customized tissue for transplant.

And it has spurred a new generation of laboratory studies into other illnesses, including schizophrenia, which may lead to new treatments.

Basically, Gurdon, 79, and Yamanaka, 50, showed how to make the equivalent of embryonic stem cells without the ethical questions those versatile cells pose.

Once created, these "blank slate" cells can be nudged toward developing into other cell types. Skin cells can ultimately be transformed into brain cells, for example.

Just last week, scientists reported turning skin cells from mice into eggs that produced baby mice, a possible step toward new fertility treatments.

Gurdon and Yamanaka performed "courageous experiments" that challenged scientific opinion, said Doug Melton, co-director of the Harvard Stem Cell Institute.

"Their work shows ... that while cells might be specialized to do one thing, they have the potential to do something else," Melton said. It "really lays the groundwork for all the excitement about stem cell biology."

In announcing the $1.2-million award, the Nobel committee at the Karolinska Institute in Stockholm, Sweden, said the work has "revolutionized our understanding of how cells and organisms develop."

Gurdon showed in 1962 that DNA from specialized cells of tadpoles, such as skin or intestinal cells, could be used to clone more tadpoles. In 1997, the same process led to the cloning of Dolly the sheep, showing it also would work in mammals.

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2 scientists win Nobel Prize for discoveries that offer alternative to embryonic stem cells

By Nonie Arora

Medicine is about more than difficult diagnoses and cutting-edge research. Research and treatments often raise tricky moral questions.

Jeremy Sugarman Credit: Berman Institute for Bioethics

Dr. Jeremy Sugarman, the founding director for the Trent Center for Bioethics, returned to campus last week to give a talk on the ethics of stem cell research and treatment for the Humanities in Medicine Lecture Series.

Stem cells are a hot topic that have captured the imagination of people around the world, he said.

Is it better to use leftover embryos from IVF or to create them for research? Sugarman asked. He said there is little consensus on this issue, and the question remains whether there is a moral distinction between discarded embryos or those created for research purposes. There is also the thorny issue of whether it is morally acceptable to destroy embryos to create human embryonic stem cells, said Sugarman, who is now at the Berman Institute for Bioethics at Johns Hopkins University.

Amidst the controversy surrounding the moral status of embryos, there has also beenscientific controversy within the stem cell field. Sugarman spoke of Hwang Woo-Suk, who claimed to have cloned human embryos and extracted their stem cells. However, his data was fabricated, Sugarman said. Sugarman elicited laughs from the packed audience when he joked about Woo-Suks former title Supreme Scientist of Korea, an honor that was later revoked. The laughter was tempered by the understanding of how unethical it is to fake any research, but especially on this scale. Still, Sugarman says Woo-Suks example serves to show the effectiveness of peer review in realizing false claims.

Human Embryonic Stem Cells. Source: "Follow the Money The Politics of Embryonic Stem Cell Research." Russo E, PLoS Biology Vol. 3/7/2005, e234 http://dx.doi.org/10.1371/journal.pbio.0030234

Another issue many people are concerned about are chimeras organisms that have parts from two different genetic lines. Already, bone marrow transplants create human-to-human chimeras, Sugarman explained. Some people have qualms about combining materials from human and non-human animals.

Other countries differ from the U.S. in policies on what can be done with human embryonic stem cells. For instance, in Germany it is a criminal offense to destroy an embryo to create a human embryonic stem cell line. It is also illegal for a German citizen to do such work abroad, Sugarman said. He brought up this point to illustrate why local oversight within academic institutions is necessary to not only make sure that research is ethically and scientifically sound but to also be certain that researchers are being protected.

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Stem Cells' Tricky Questions

08-10-2012 20:30 England's Sir John Gurdon and Dr. Shinya Yamanaka from Japan share the 2012 Nobel Prize in medicine for work on stem cells, revealing that mature cells can be reverted into primitive cells. Ray Suarez talks to Harvard Stem Cell Institute's Dr. David Scadden, who explains the implications and applications for stem cell medicine.

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Stem Cell Scientists Win Nobel Prize in Medicine - Video