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Following a heart attack,
millions of cells that provide contractile function to the heart are destroyed.
By transplanting embryonic stem cells in the postinfarction hearts of
rats, a CNRS research team succeeded in directing the differentiation
of cells into cardiomyocytes or heart cells. The experiment revealed perfect
tolerance by the host animal and recovery of heart function. Although
much work remains to be done, particularly on human embryonic stem cells,
these results present an alternative to transplants of the myocardium
that involve major surgery. The experiment was carried out by the "ES(1)
and heart differentiation cell" team, under the supervision of Michel
Pucéat, at the CNRS Macromolecular Biochemistry Research Center(2)
, working in partnership with André Terzic's team at the MAYO(3)
Clinic (Minnesota, United States).
Heart failure is one of the
consequences of many different types of heart disease (myocardial infarction,
high blood pressure, increased blood cholesterol level, cardiomyopathy,
etc.). It affects thousands of French people and is responsible for a
very large part of the mortality rate. 176,000 people die every year of
cardiovascular disease in France(4) . Due to the lack
of adequate drug treatment, this pathology most often results in a heart
transplant. However, patients must undergo major surgery and are required
to follow a restrictive anti-rejection treatment with dangerous long-term
side effects. Moreover, not all patients (diabetics, for example) qualify
for a transplant. Finally, the number of donors remains considerably limited
and cannot meet the present demand for transplants in our country.
The heart is made up of about two billion cells, each one forming a contractile
unit. These cells all contract together, keeping the heart pump going.
When a heart attack occurs, millions of cells are lost because the heart
is an organ that does not have the capacity to regenerate itself. The
resulting loss of mechanical function of the myocardium is responsible
for the failure, which develops over the years following infarction. Grafting
of embryonic stem cells that have the potential to generate all types
of tissues and whose purpose could be predetermined, can also replace
areas destroyed during a heart attack.
A new "cellular" therapeutic pathway
Researchers have recently discovered that the myocardium in animals is
a propitious site for transplanting embryonic stem cells that, by spontaneously
differentiating into heart cells, lead to the total recovery of mechanical
function. By using differentiation factors naturally present in the healthy
or postinfarction myocardium, they have shown that it is possible to direct
the differentiation of murine embryonic stem cells into cardiomyocytes.
When transplanted in vivo in infarcted rat myocardium following an experimentally
induced heart attack, stem cells spontaneously differentiated into cardiomyocytes.
By experimentally blocking the activation of the cell receptors in these
differentiation factors, both in vitro and in vivo, stem cells are no
longer capable of differentiating but, on the contrary, proliferate in
a non-differentiated state.
Researchers have thus shown that these same endogenous growth factors
are responsible for the spontaneous differentiation of stem cells in the
myocardium.
The transplanting of stem cells makes it possible to restock the ischaemic
(lacking in oxygen) and fibrotic areas of the postinfarction heart and
leads to total recovery of mechanical function (of the pump) of the unhealthy
myocardium, with no sign of rejection of the grafted cells. Stem cells
were not even rejected eight months following heterologous grafts(5)
, demonstrating perfect tolerance by the host animal.
Although much work remains to be done, particularly on human embryonic
stem cells, these results offer a real possibility for cell therapy for
heart failure in humans.
This research, financed by the French Myopathy Association
and the Foundation of France was published on October 1st 2002 in the
FASEB Journal (volume 16, pp. 1558-1566), the journal of the
Federation of American Societies for Experimental Biology ("Stem
cell differentiation requires a paracrine pathway in the heart",
by Atta Behfar, Leonid V. Zingman, Denice M. Hodgson, Jean-Michel Rauzier,
Garvan C. Kane, André Terzic, Michel Pucéat).
(1)ES for embryonic stem
(2)The Macromolecular Biochemistry Research Center directed
by Marcel DOREE was created in 1998 and includes 96 people of whom 41
are professional researchers (CNRS, INSERM, university-affiliated), in
Montpellier. Its research activities are open to the public through contractual
relationships and partnerships with public and private organisations.
http://xerxes.crbm.cnrs-mop.fr/present.html
(3)The MAYO Clinic is one of the largest hospital research
centers in the United States and the first in cardiology.
(4)Source: INSERM 2000
(5)Heterologous graft: from one species to another, in
this case, the cells of mice introduced into the rat.
Researcher
contact:
Michel Pucéat
Centre de Recherches de Biochimie Macromoléculaire
Tel: +33 4 67 61 34 32
puceat@crbm.cnrs-mop.fr
Press contact:
Nathalie Tramunt
Tel : +33 1 44 96 46 06
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