In a novel effort to simplify and speed up safe human
stem cell research, Johns Hopkins has set up a "one-stop
shop" to preserve, create, supply and test high-quality
cell lines for its own researchers now and the greater
scientific community later.
The privately funded Stem Cell Resource Center, housed
for now within the School of Medicine's
Institute for Cell Engineering, offers streamlined and
centralized handling of cell lines and requests to use them
and is expected to cut wait times and paperwork
substantially, according to Chi V. Dang, the school's vice
dean for research and head of ICE.
In tandem with the opening of the center, Hopkins has
appointed an eight-person embryonic stem cell research
oversight committee modeled on guidelines set forth in 2005
by the National Academies. Similar to institutional review
boards that oversee the safety of human subjects in
research, the ESCRO committee's charge is to ensure that
all human stem cell experiments conducted at the university
are safe.
"It's frankly astonishing that no other place has done
the much-needed, head-to-head comparison of the existing
stem cell lines to fully describe them and make sure
they're safe to use," Dang said. "This isn't the 'sexy'
part of stem cell work, but it's critical because this
research aims at developing stem cell treatment for use in
people, and ESCRO is going to make sure to every extent
possible that such use at Hopkins is safe."
The center and ESCRO will call on Hopkins experts to
screen all cell lines for alterations or mutations that
might compromise their quality or signal danger. For
example, scientists from the
McKusick-Nathans Institute of Genetic Medicine and
Center for Epigenetics of the Institute of Basic Biomedical
Sciences will examine DNA sequences and chromosomes in each
cell line for alterations that look like cancer or other
inherited diseases.
Last year, a team led by researchers at the
McKusick-Nathans Institute reported that human embryonic
stem cell lines accumulate changes in their genetic
material over time. Cells grown in the lab longer were
worse off, containing the wrong number of chromosomes,
changes in the marks that control genes or changes in the
DNA sequence. While the precise effects of these changes
aren't known, some resemble those seen in cancer cells.
Whether the changes affect the stem cells' abilities to
become other cell types also is unknown.
Within the center, experts in genomics — the
study of genes and their functions — will develop
molecular tool kits for turning on or off genes that coax
stem cells to develop into specific cell types, and experts
in microscope imaging will create and test better ways to
mark the cells so that they can be observed and followed as
they grow and develop.
"We're convinced that such services will bring a
stunning level of confidence and security to stem cell
research at Hopkins, so much so that scientists will be
able to work more quickly," Dang said. With plans to apply
for funds from Maryland's new stem cell initiative, Dang
added, the center hopes to open its services to non-Hopkins
scientists in the state and more widely next year.
Beyond researcher convenience and safety,
centralization of services within the center should mean
economies of scale that will lead to better use of dollars
and time, Dang noted. "These are core operations that can't
always be done by a single lab, and now that lab doesn't
have to reinvent every wheel to do important work," he
said.
The center's scientists also will establish new cell
lines and study how they change over time, and when or
under what conditions they lose genomic integrity, Dang
said.
"We know of many researchers who would like to venture
into stem cell science but don't in great measure because
of the immense bureaucratic burden of paperwork required to
gain access to individual cell lines by contract or
material transfer agreements," he said. "The center will do
all that for the entire university, so that as far as any
individual investigator can tell, it will be free access."
With start-up support from a small portion of a $100
million anonymous gift to the university earlier this year,
the center first will store a collection of adult and
embryonic stem cell lines, some approved for studies that
have federal funding and some not. The center also will
keep tabs on the funding used to support research on all
the cells it provides to ensure compliance with federal
laws.
Human embryonic stem cells are obtained from extra
embryos created during in vitro fertilization. Because the
cells can become any type of cell in the body, they may one
day treat or cure diseases such as Parkinson's or type I
diabetes. According to policy established by President
Bush, only human embryonic stem cell lines created before 9
p.m. ET on Aug. 9, 2001, can be used in federally funded
research. The cell lines that currently meet that
eligibility requirement are not suitable for use in any
future human trials because they were initially grown on
mouse cells and therefore might harbor mouse-specific
viruses.
As the center ramps up its services, the ESCRO
committee — under the leadership of Jeremy Sugarman,
professor in the
Berman
Bioethics Institute, and Carol Greider, the Daniel
Nathans Professor and director of
Molecular Biology and
Genetics in the Institute of Basic Biomedical Sciences
— will set universitywide standards on experiments
performed at Johns Hopkins.
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