| > |
By manipulating a critical cell-to-cell
signaling pathway, researchers at the University of Pennsylvania
School of Medicine have successfully increased the number
cells required for the normal development of right-sided structures
in the heart, including the right ventricle. |
| > |
Penn scientists were able to increase the
numbers of a cardiac stem cell population, called Isl-1 positive
cardiac progenitors, in the developing embryo and in tissue grown
in a culture dish by activating the Wnt pathway. |
| > |
The finding suggests a potential therapeutic
strategy whereby influencing this pathway would be used to generate
specialized heart cells to repair or replace cells damaged by
cardiac disease. |
| > |
The research will be reported in the Journal
of Clinical Investigation’s online edition on June
21, 2007 and will appear in the print edition on July 2, 2007. |
(PHILADELPHIA) — By
manipulating a critical cell-to-cell signaling pathway, researchers
at the University of Pennsylvania School of
Medicine have successfully
increased the number cells required for the normal development
of right-sided structures in the heart, including the right
ventricle.
Penn scientists were able to increase the numbers of a cardiac
stem
cell population, called Isl-1 positive cardiac progenitors,
in the developing embryo and in tissue grown in a culture dish
by activating the Wnt pathway. The finding suggests a potential
therapeutic strategy whereby influencing this pathway would be
used to generate specialized heart cells to repair or replace cells
damaged by cardiac
disease.
The research will be reported in the Journal of Clinical Investigation’s online edition on June 21, 2007 and will appear in the print edition
on July 2, 2007.
“This is the first evidence that the Wnt signaling pathway plays a crucial
role in the generation of cells that can differentiate into functioning cardiac
structures,” said Edward
E. Morrisey, PhD, Associate
Professor of Medicine and Cell
and Developmental Biology and the senior author
on the paper. “Our
studies indicate a direct link between Wnt and a specific family of progenitor
cells that transform themselves into critical structures in the heart during
development.”
Although scientists know that the Isl-1 positive progenitor cells
play an important role in the development of the right side of
the heart including the right ventricle, the molecular pathways
regulating these critical cells are poorly understood. Isl-1
progenitors have been shown to have the capacity of self-renewal
and to differentiate into specialized cells including cardiac myocytes and smooth
muscle cells, thus exhibiting the characteristics of
tissue specific stem cells. Morrisey and his team first demonstrated
that the Wnt signaling pathway is active in Isl-1 progenitors.
The next step taken by the Penn researchers was to increase or
decrease the activity of the Wnt pathway to increase or decrease
the number of Isl-1 progenitors respectively, the first time this
has been shown in a mouse model. This resulted in the loss
of the right ventricle, which Isl-1 progenitors contribute to,
whereas the left ventricle, which Isl-1 progenitors do not contribute
towards, was spared.
The scientists also noticed that in addition to an increase in
the numbers of Isl-1 positive cells, there was also an increase
in a class of growth factors that has been shown to act cooperatively
with Wnt signaling to regulate progenitor cells in other tissues.
Having determined that the class of proteins called Fibroblast
Growth Factors or FGFs worked downstream from Wnt signaling, the
Penn scientists went on to show that at least one of the FGF ligands,
FGF10, known to directly impact the development of the heart, was
a direct target of Wnt signaling.
“Isl-I progenitors are present in the early
postnatal heart,
but disappear with progressing age,” says Dr. Morrisey. “Given
the extreme rarity of these cells and their ability to act as progenitors
of mature cardiac myocytes, the capacity of Wnt signaling to expand
this population may prove to be useful in future work to harness
the ability of these cells to regenerate damaged cardiac tissue.”
###
PENN Medicine is a $2.9 billion enterprise
dedicated to the related missions of medical education, biomedical
research, and high-quality patient care. PENN Medicine consists
of the University of Pennsylvania School of Medicine (founded in
1765 as the nation's first medical school) and the University of
Pennsylvania Health System.
Penn's School of Medicine is ranked #2 in the nation for receipt
of NIH research funds; and ranked #3 in the nation in U.S. News
& World Report's most recent ranking of top research-oriented
medical schools. Supporting 1,400 fulltime faculty and 700 students,
the School of Medicine is recognized worldwide for its superior
education and training of the next generation of physician-scientists
and leaders of academic medicine.
The University of Pennsylvania Health System includes three hospitals,
all of which have received numerous national patient-care honors [Hospital
of the University of Pennsylvania; Pennsylvania Hospital, the nation's
first hospital; and Penn Presbyterian Medical Center]; a faculty practice
plan; a primary-care provider network; two multispecialty satellite
facilities; and home care and hospice.
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.
The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.
The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.