twitter Tweet

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

New findings demonstrate potential to treat a wide variety of disorders that affect myelin

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 Papé 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.

In a study conducted by clinical researchers at the University of California San Francisco and published in the same online issue of Science Translational Medicine (Gupta et. al), the human neural stem cells were also tested in a small number of patients with a rare childhood myelin disorder where the MRI was detecting signals from the brain consistent with myelin formation. Before MRI, there wasn’t a way to confirm new myelin without a brain biopsy or an autopsy. The USCF researchers report the study results strongly support that the MRI findings in the patients were due to new myelin.

“These findings provide us with much greater confidence that going forward, a wide variety of myelin disorders might be candidates for therapy. Of course, each condition varies in terms of severity, how fast it progresses and the degree of brain injury it causes. This must all be taken into consideration as neurologists and stem cell biologist work to make further advances for these challenging brain disorders,” Back said.

This study was supported by National Institutes of Health grants P51RR000163 and NCRR P51 RR000113; National Institute of Neurological Disorders and Stroke grants 1RO1NS054044 and R37NS045737-06S1/06S2 and 1F30NS066704; a Bugher Award from the American Heart Association; March of Dimes Birth Defects Foundation; and Friends of Doernbecher Children’s Hospital Foundation.

Disclosure: Dr. Back was previously a paid consultant to StemCells Inc.


Oregon Health & Science University and its children’s hospital, OHSU Doernbecher Children’s Hospital, are nationally recognized for their research and clinical emphasis on white matter disorders of the brain. Several OHSU and OHSU Doernbecher groups contributed to this study as a collaborative team led by Stephen A. Back, M.D., Ph.D., pediatric neurologist and director of the Pediatric Neuroscience Research Program in the Papé Family Pediatric Research Institute at OHSU Doernbecher Children’s Hospital.

Dr. Back has a long-standing research program focused on white matter disorders in children and adults that is supported by a Javits Neuroscience Investigator Award from the National Institute of Neurological Disorders and Stroke. Chris Kroenke, Ph.D., an associate scientist in OHSU’s Advanced Imaging Research Center led the team that performed the high-field MRI studies. Dr. Kroenke has the specialized expertise required to analyze MRI signals coming from the developing brain.

Larry Sherman, Ph.D., a senior scientist in the Oregon National Primate Research Center, and Steve Matsumoto, Ph.D., an associate professor in OHSU School of Dentistry, performed studies that confirmed functional myelin was generated by the stem cells by means of nerve conduction studies in slices of brain tissue from the animals that received the transplants. Drs. Sherman and Matsumoto are long-time collaborators with Dr. Back and have made major advances to the understanding of human white matter disorders in children and adults.

Previous Story Knight Cancer Institute deputy director selected for prostate cancer Dream Team Next Story OHSU receives $1 million grant to develop innovative Electronic Health Record simulations