-- A precise method has been developed that prospectively
isolates just the stem cells that can treat multiple sclerosis and
childhood diseases caused by the brain's inability to make
--After analzying genes in different stem cell types, the
scientists searched for and found the genes that were most likely
to differentiate into stem cells that make myelin.
--The human stem cells were then successfully injected into the
brains of mice with MS.
--The new method brings the prospect of clinical trials that
much closer, the scientists say.
BUFFALO, N.Y. – The prospect of doing human clinical
trials with stem cells to treat diseases like multiple sclerosis
may be growing closer, say scientists at the University at Buffalo
and the University at Rochester, who have developed a more precise
way to isolate stem cells that will make myelin.
Myelin is the crucial fatty material that coats neurons and
allows them to signal effectively. The inability to make myelin
properly is the cause of MS as well as rare, fatal, childhood
diseases, such as Krabbe's disease.
The research, published online and in the October issue of
Nature Biotechnology, overcomes an important barrier to the use of
stem cells from the brain in treating demyelinating diseases.
Until now, it has been difficult to separate out the right
progenitor cells – the ones that will develop into cells that
make myelin, explains Fraser Sim, PhD, first and co-corresponding
author on the paper and assistant professor in the Department of
Pharmacology and Toxicology in the UB School of Medicine and
Biomedical Sciences; he did much of the work while he was a
researcher at Rochester.
"Characterizing and isolating the exact cells to use in stem
cell therapy is one key to ultimately having success," said Sim.
"You need to have the right cells in hand before you can even think
about getting to a clinical trial to treat people. This is a
Sim and Rochester graduate student Crystal McClain ran extensive
analyses looking at gene activity in different types of stem cells,
leading to the conclusion that stem cells carrying a protein known
as CD140a on their surface seemed to be most likely to become
oligodendrocytes – the type of brain cell that makes
The UB and Rochester scientists then injected the cells into the
brains of mice that were born without the ability to make myelin.
Twelve weeks later, the cells had become oligodendrocytes and had
coated more than 40 percent of the brain's neurons with myelin
– a four-fold improvement over the team's previous results
published in Cell Stem Cell and Nature Medicine.
"These cells are our best candidates right now for someday
helping patients with M.S., or children with fatal hereditary
myelin disorders," said Steven Goldman, MD, PhD, co-author, the
leader of the team and professor and chair of the Department of
Neurology at the University of Rochester Medical Center. "These
cells migrate more effectively throughout the brain, and they
myelinate other cells more quickly and more efficiently than any
other cells assessed thus far. Now we finally have a cell type that
we think is safe and effective enough to propose for clinical
An eventual treatment of a disease like M.S. might involve
injecting stem cells to create myelin in the brains of
"Another approach," says Sim, "might involve using certain
medications to turn on these cells already present in the brains of
patients and thereby create new myelin. The use of the new
techniques described in this work will permit us to better
understand how human cells behave in the brain and help us predict
which medications may be successful in the treatment of myelin
The new approach may also be applicable to Krabbe's Disease, Sim
says, which also involves the breakdown of myelin. Sim, who came to
UB in 2009, is actively collaborating on related work with
researchers at the Hunter James Kelly Research Institute, a
partnership between UB and the Hunter's Hope Foundation and located
in UB's New York State Center of Excellence in Bioinformatics and
In addition to Sim, McClain, and Goldman, other authors of the
paper include Martha Windream, assistant professor in the
Department of Neurology and technical associates Steve Schanz and
Tricia Protack, all of the University of Rochester. The work was
supported by the National Institute of Neurological Disorders and
Stroke, the National Multiple Sclerosis Society, the New York State
Stem Cell Research Board, the Adelson Medical Research Foundation
and the Mathers Charitable Foundation.