Stem Cells as a therapy for myocardial infarction in animal models
Creators: name: Fiumana, Emanuela <1975>
Publisher: name: Alma Mater Studiorum - Università di Bologna
Year: 2008
Subjects: BIO/10 Biochimica

description: Advances in stem cell biology have challenged the notion that infarcted myocardium is
irreparable. The pluripotent ability of stem cells to differentiate into specialized cell lines began
to garner intense interest within cardiology when it was shown in animal models that
intramyocardial injection of bone marrow stem cells (MSCs), or the mobilization of bone
marrow stem cells with spontaneous homing to myocardium, could improve cardiac function and
survival after induced myocardial infarction (MI) [1, 2]. Furthermore, the existence of stem cells
in myocardium has been identified in animal heart [3, 4], and intense research is under way in an
attempt to clarify their potential clinical application for patients with myocardial infarction. To
date, in order to identify the best one, different kinds of stem cells have been studied; these have
been derived from embryo or adult tissues (i.e. bone marrow, heart, peripheral blood etc.).
Currently, three different biologic therapies for cardiovascular diseases are under investigation:
cell therapy, gene therapy and the more recent “tissue-engineering” therapy .
During my Ph.D. course, first I focalised my study on the isolation and characterization of
Cardiac Stem Cells (CSCs) in wild-type and transgenic mice and for this purpose I attended, for
more than one year, the Cardiovascular Research Institute of the New York Medical College, in
Valhalla (NY, USA) under the direction of Doctor Piero Anversa. During this period I learnt
different Immunohistochemical and Biomolecular techniques, useful for investigating the
regenerative potential of stem cells.
Then, during the next two years, I studied the new approach of cardiac regenerative medicine
based on “tissue-engineering” in order to investigate a new strategy to regenerate the infracted
myocardium. Tissue-engineering is a promising approach that makes possible the creation of
new functional tissue to replace lost or failing tissue. This new discipline combines isolated
functioning cells and biodegradable 3-dimensional (3D) polymeric scaffolds. The scaffold
temporarily provides the biomechanical support for the cells until they produce their own
extracellular matrix. Because tissue-engineering constructs contain living cells, they may have
the potential for growth and cellular self-repair and remodeling. In the present study, I examined
whether the tissue-engineering strategy within hyaluron-based scaffolds would result in the
formation of alternative cardiac tissue that could replace the scar and improve cardiac function
after MI in syngeneic heterotopic rat hearts. Rat hearts were explanted, subjected to left coronary
descending artery occlusion, and then grafted into the abdomen (aorta-aorta anastomosis) of
receiving syngeneic rat. After 2 weeks, a pouch of 3 mm2 was made in the thickness of the
ventricular wall at the level of the post-infarction scar. The hyaluronic scaffold, previously
engineered for 3 weeks with rat MSCs, was introduced into the pouch and the myocardial edges
sutured with few stitches. Two weeks later we evaluated the cardiac function by M-Mode
echocardiography and the myocardial morphology by microscope analysis.
We chose bone marrow-derived mensenchymal stem cells (MSCs) because they have shown
great signaling and regenerative properties when delivered to heart tissue following a myocardial
infarction (MI). However, 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, that’s why we decided to combine MSCs with a biopolimeric scaffold.
At the end of the experiments we observed that the hyaluronan fibres had not been
substantially degraded 2 weeks after heart-transplantation. Most MSCs had migrated to the
surrounding infarcted area where they were especially found close to small-sized vessels. Scar
tissue was moderated in the engrafted region and the thickness of the corresponding ventricular
wall was comparable to that of the non-infarcted remote area. Also, the left ventricular
shortening fraction, evaluated by M-Mode echocardiography, was found a little bit increased
when compared to that measured just before construct transplantation. Therefore, this study
suggests that post-infarction myocardial remodelling can be favourably affected by the grafting
of MSCs delivered through a hyaluron-based scaffold