Cardiac Stem Cell Therapy Closer To Reality
Main Category: Cardiovascular / Cardiology
Also Included In: Stem Cell Research; Conferences
Article Date: 28 Dec 2007 - 1:00 PST
Since the year 2000, much has been learned about the potential for
using transplanted cells in therapeutic efforts to treat varieties of
cardiac disorders. With many questions remaining, the current issue
of CELL TRANSPLANTATION (Vol.16 No. 9), The Proceedings of the Third
Annual Conference on Cell Therapy for Cardiovascular Disease,
presents research aimed at answering some of them. Eleven papers were
included in this issue; the four below represent a sample.
Bench to Bedside
"Cardiac stem cell therapy involves delivering a variety of cells
into hearts following myocardial infarction or chronic
cardiomyopathy,
therapy at the University of Pittsburgh Medical Center and lead
author of an overview and introductory article, Cardiac Stem Cell
Therapy from Bench to Bedside. "Many questions remain, such as what
types of cells may be most efficacious. Questions about dose,
delivery method, and how to follow transplanted cells once they are
in the body and questions about safety issues need answers. The
following studies, contribute to the growing body of data that will
move cell transplantation for heart patients closer to reality."
According to Patel, special editor for this issue, suitable sources
of cells for cardiac transplant will depend on the types of diseases
to be treated. For acute myocardial infarction, a cell that reduces
myocardial necrosis and augments vascular blood flow will be
desirable. For heart failure, cells that replace or promote
myogenesis, reverse apoptopic mechanisms and reactivate dormant cell
processes will be useful.
"Very little data is available to guide cell dosing in clinical
studies," says Patel. "Pre-clinical data suggests that there is a
dose-dependent improvement in function."
Patel notes that the availability of autologous (patient self-
donated) cells may fall short.
Determining optimal delivery methods raise issues not only of dose,
but also of timing. Also, assessing the fate of injected cells
is "critical to understanding mechanisms of action."
Will cells home to the site of injury" Labeling stem cells with
durable markers will be necessary and new tracking markers may need
to be developed.
Improved cell survival drugs
Adult bone marrow-derived mensenchymal stem cells (MSCs) have shown
great signaling and regenerative properties when delivered to heart
tissues following a myocardial infarction (MI). However, the poor
survival of grafted cells has been a concern of researchers. Given
the poor vascular supply after a heart attack and an active
inflammatory process, grafted cells survive with difficulty.
Transmyocardial revasularization (TMR), a process by which channels
are created in heart tissues by laser or other means, can enhance
oxygenated blood supply.
"We hypothesized that using TMR as a scar pretreatment to cell
therapy might improve the microenvironment to enhance cell retention
and long-term graft success," said Amit N. Patel, lead author of a
study titled Improved Cell Survival in Infarcted Myocardium Using a
Novel Combination Transmyocardial Laser and Cell Delivery
System. "TMR may act synergistically with signaling factors to have a
more potent effect on myocardial remodeling."
Patel and colleagues, who used a novel delivery system to disperse
cells in the TMR-generated channels in an animal model, report
significant cell survival in the TMR+Cell group versus Cells or TMR
alone. The researchers speculated that there was an increase in local
production of growth factors that may have improved the survival of
transplanted cells.
Stem cells depolarize
Recent studies have suggested that there are stem cells in the heart.
In this study, researchers engineered mesenchymal stem cells (MSC) to
over express stromal cell-derived factor-1 (SDF-1), a chemokine.
"Our study suggests that the prolongation of SDF-1 expression at the
time of an acute myocardial infarction (AMI) leads to the recruitment
of what may be an endogenous stem cell in the heart," says Marc Penn,
MD, PhD, director of the Skirball Laboratory for Cardiovascular
Cellular Therapeutics at the Cleveland Clinic Foundation. "These
cells may contribute to increased contractile function even in their
immature stage."
In the study titled SDF-1 Recruits Cardiac Stem Cell Like Cells that
Depolarize in Vivo, researchers concluded that there is a natural but
inefficient stem cell-based repair process following an AMI that can
be manipulated through the expression of key molecular pathways. The
outcome of this inefficient repair can have a significant impact on
the electrical and mechanical functions of the surviving myocardium.
Grafting bioartifical myocardium for myocardial assistance
While the object of cell transplantation is to improve ventricular
function, cardiac cell transplantation has had limited success
because of poor graft viability and low cell retention. In a study
carried out by a team of researchers from the Department of
Cardiovascular Surgery, Pompidou Hospital, a matrix seeded with bone
marrow cells (BMC) was grafted onto the infarcted ventricle to help
support and regenerate post-ischemic lesions.
"Our study demonstrated that bone marrow cell therapy associated with
the surgical implantation onto the epicardium of a cell-seeded
collagen type 1 matrix prevented myocardial wall thinning, limited
post-ischemic remodeling and improved diastolic function," says Juan
Chachques, MD, PhD, lead author for Myocardial Assistance by Grafting
a New Bioartificial Upgraded Myocardium (MAGNUM Clinical Trial): One
year follow-up.
"The use of the biomaterial appears to create a micro atmosphere
where both exogenous and endogenous cells find an optimal
microenvironment to repair tissues and maintain low scar production,"
explains Chachques.
According to Chachques, the favorable effects may be attributed to
several mechanisms. The BMC seeded in the collagen matrix may be
incorporated into the myocardium through epicardial channels created
at the injection sites. Too, the cell-seeded matrix may help prevent
apoptosis.
"This biological approach is attractive because of its potential for
aiding myocardial regeneration with a variety of cell types,"
concluded Chachques.
Those cell types include skeletal myoblasts, bone marrow-derived
mensenchymal stem cells, circulating blood-derived progenitor cells,
endothelial and mesothelial cells, adipose tissue stem cells and,
potentially, embryonic stem cells.
"Cardiac stem cell repair is one of the most important new areas of
research today," says Cell Transplantation editor Paul Sanberg, PhD,
DSc. "This special issue illustrates important new findings and the
significant efforts being taken to develop these therapies and move
them from the scientist's bench to the bedside where in clinical
practice they can make a difference in the lives of patients."
CELL TRANSPLANTATION - The Regenerative Medical Journal
http://www.cognizan
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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