Stem Cells Improve Motor Function in Brain Injuries
stem cells, transplanted into injured brains, survive, proliferate,
and improve brain function in laboratory models according to
research based at the School of Medicine. The findings, published
in the October edition of the journal Neurosurgery,
suggest that stem cells could provide the first clinical therapy
to treat traumatic brain injuries. Traumatic brain injuries
occur in two million Americans each year and are the leading
cause of long-term neurological disability in children and
of neural stem cells in mice three days after brain injury
promotes the improvement of specific components of motor function," said
Dr. Tracy K. McIntosh, professor of neurosurgery, Director
of Penn's Head Injury Center, and senior author of the study. "More
importantly, these stem cells respond to signals and create
replacement cells: both neurons, which transmit nerve signals,
and glial cells, which serve many essential supportive roles
in the nervous system."
stem cells are blank slates, able to become any type of body
cells, then neural stem cells (NSCs) are slates with the basics
of neurology already written on them, waiting for signals in
the nervous system to fill in the blanks. The NSCs used by
Dr. McIntosh and his colleagues were cloned from mouse progenitor
cells and grown in culture. The advantage of NSCs exists in
their ability to easily incorporate themselves into their new
environment in ways other types of transplants could not.
humans, traumatic brain injury is associated with disabilities
affecting mobility, motor function and coordination. Following
NSC transplantation in mice, the researchers used simple tests
to determine motor skills. They found that mice with transplanted
NSCs recovered much of their physical ability. The transplanted
NSCs, however, seemed to have little effect in aiding recovery
of lost cognitive abilities.
ultimate goal, of course, is to translate what we have learned
into a therapy for humans," said Dr. McIntosh. Neural
transplantation has been suggested to be potentially useful
as a therapeutic intervention in several central nervous system
diseases including Parkinson's disease, Huntington's disease,
ischemic brain injury, and spinal cord injury. While Dr. McIntosh
is impressed with the results of NSC transplants in mice, similar
trials for humans are not expected in the near future.
lead author on this study is Dr. Peter Reiss, a visiting fellow
from the University of Cologne working in Dr. McIntosh's laboratory.
Much of the work was performed in collaboration with the laboratory
of Dr. Evan Y. Snyder, Harvard Medical School.
contributing researchers from the department of neurosurgery
at Penn include, Dr. Chen Zhang, Dr. Kathryn E. Saatman, Dr.
Helmut L. Laurer, Dr. Luca G. Longhi, Dr. Ramesh Raghupathi,
Dr. Philipp Lenzlinger, Dr. Jonathan Lifshitz, Dr. John Boockvar,
Dr. Grant Sinson, and Dr. M. Sean Grady. Other contributing
researchers include Dr. Edmund Neugebauer, University of Cologne,
Germany and Dr. Yang D. Teng, Harvard Medical School.
Patients Die in Hospitals with Lower Nurse Staffing
the first study of its kind, Penn researchers have determined
that patients who have common surgeries in hospitals with the
worst nurse staffing levels have up to a 31% increased chance
of dying. More nurses at the bedside could save thousands of
patient lives each year, as reported last week in The Journal
of the American Medical Association (JAMA).
researchers found that every additional patient in an average
hospital nurse's workload increased the risk of death in surgical
patients by 7%. Patients with life-threatening complications
were also less likely to be rescued in hospitals where nurses'
patient loads were heavier. The findings impact the national
report greater job dissatisfaction and emotional exhaustion
when they're responsible for more patients than they can safely
care for. Failure to retain nurses contributes to avoidable
patient deaths," said Dr. Linda Aiken, director of the
Center for Health Outcomes and Policy Research at the School
of Nursing. "Patients facing planned hospitalization should
inquire about nurse-to-patient ratios and choose their hospitals
accordingly." Hospital nurse staffing levels vary widely,
usually from four patients per nurse on most unit types to
up to ten or more.
the Penn nursing researchers found that:
all hospitals in the nation staffed at eight patients per nurse
rather than four, the risk of hospital deaths would increase
by 31 percent, roughly translating to as many as 20,000 avoidable
deaths in the U.S. annually. Some 4 million surgeries like
the ones studied are performed each year.
too few nurses may actually cost more because of the high costs
of replacing burnt-out nurses and higher costs of caring for
patients with poor outcomes.
two patients to a nurse already caring for four, increases
the risk of death by 14 percent, adding four increases the
risk by 31 percent.
is clear that nurses are saving lives," said Dr. Aiken. "Nurses
are the front line of surveillance and early detection of potentially
report, "Hospital Nurse Staffing and Patient Mortality,
Nurse Burnout, and Job Dissatisfaction," concluded in
the October 23/30 issue of JAMA: "when taken together,
the impacts of staffing on patient and nurse outcomes suggest
that by investing in registered nurse staffing, hospitals may
avert both preventable mortality and
problems with low
nurse retention in hospital practice."
study, funded by the National Institute of Nursing Research
of the National Institutes of Health, examined data collected
from 168 hospitals, 232,342 surgical patients, and 10,184 nurses
in Pennsylvania from 1998 to 1999. The researchers examined
data on relatively common general surgeries (e.g. gall bladder),
orthopedic surgeries (e.g. knee or hip replacement), and vascular
surgeries, excluding cardiac surgery such as coronary bypass.
Some routine but emergency surgeries were included, such as
that Regulates Development of Heart Cells Identified
at the School of Medicine have identified and described a small
gene that regulates the delicate balance involved in the healthy
growth and replication of heart muscle cells.
finding is likely to be important for our understanding of
the causes of congenital heart disease. It is also relevant
to our attempts to regrow damaged heart muscle," said
the corresponding author of the study, Dr. Jonathan A. Epstein,
of the departments of medicine and cell & developmental
biology. The study appeared in the September 20 issue of the
newly identified heart gene, Hop (an acronym for homeodomain
only protein), is a small protein that lacks certain residues
required for DNA binding, but is activated early in fetal development
and continues modulating the expression of cardiac-specific
genes throughout life. Hop appears to bind directly to another
important regulator of development, serum response factor (SRF),
and block SRF from binding to DNA. By inhibiting the expression
of SRF, Hop protects cardiac muscle cells from over-development,
and from developing fatal abnormalities.
has been a lot of effort to try to determine how SRF is regulated
in different tissues," Dr. Epstein said. "Now we
see that Hop plays a vital part."
study was funded by the National Institutes of Health, the
American Heart Association, and the W.W. Smith Foundation.
who participated in the research are: Dr. Fabian Chen,
Dr. Hyun Kook, Dr. Rita Milewski, Dr. Aaron D. Gitler, Dr.
Min Min Lu, Dr. Jun Li, Dr. Ronniel Nazarian, Dr. Robert Schnepp,
Dr. Kuangyu Jen, Dr. Greg Runke, and Dr. Mary C. Mullins, all
of Penn; Dr. Christine Biben, Dr. Joel P. Mackay, Dr. Jiri
Novotny, all of the Victor Chang Cardiac Research Institute,
Carlinghurst, Australia; Dr. Robert Schwartz, of Baylor
College of Medicine, Houston, TX, and Dr Richard P. Harvey,
of the Chang Institute and the University of New South Wales,
Gene Allows Stem Cells to Remain Stem Cells
the search to understand the nature of stem cells, researchers
at the the School of Medicine have identified a regulatory
gene that is crucial in maintaining a stem cell's ability to
self-renew. According to their findings, the Foxd3 gene is
a required factor for pluripotency--the ability of stem cells
to turn into different types of tissue--in the mammalian embryo.
Their research was presented in the October 15 issue of the
journal Genes and Development.
cells represent a unique tissue type with great potential for
disease therapy, but if we are to use stem cells then we ought
to know the basis of their abilities," said Dr. Patricia
Labosky, assistant professor in the department of cell and
developmental biology. "Among the stem cell regulatory
genes, it appears that Foxd3 gene expression keeps stem cells
from quickly differentiating--that is, developing into different
types of tissue--holding back the process so that an embryo
will have enough stem cells to continue developing normally."
findings implicate Foxd3 as one of the few genes serving as
a master switch' of the developing embryo," said
Dr. Labosky. "These genes determine the fate of cells
by turning on or off other genes in response to signals in
the embryo." Foxd3 joins previously identified genes,
such as Oct4, Fgf4, and Sox2, which control the pluripotency
of embryonic stem cells in the early stages of embryogenesis.
In their experiments, Dr. Labosky and her colleagues found
that these genes are still expressed despite the lack of Foxd3.
This suggests Foxd3 functions either downstream of Oct4, Fgf4
and Sox2, or along a parallel pathway.
researchers determined that normal embryonic development can
be restored by adding non-mutant embryonic stem cells to the
Foxd3-mutant embryos, indicating that Foxd3 acts in the inner
cell mass and its derivatives. According to Dr. Labosky, Foxd3
is a key regulator of mammalian stem cells, with a clear counterpart
in humans. Foxd3 gene expression is a diagnostic characteristic
of human embryonic stem cells, suggesting that the gene may
function in a similar fashion in mouse and human cells.
Almanac, Vol. 49, No. 10, October 29, 2002