Research

LCMC
research activity is focused on defining the myocardial pathophysiology and in
setting up new concepts and procedures to cure cardiac muscle diseases.

In
particular, two aspects are actively investigated.

1) Effects
of the Omega-3 polyunsaturated fatty acids (PUFAs) on the cardiac muscle

Omega-3
PUFAs are well known for their beneficial effects in the secondary prevention
of the cardiac ischemic disease. However, the mechanisms thru which these
beneficial effects are executed remain not understood yet. LCMC has given a
substantial contribution to the understanding of such mechanisms. In fact, it
has been possible to reveal that Omega-3 PUFAs exert a potent epigenetic effect
that, very likely, sustain caveolin-3 expression and localization into
caveolae. This mechanism hampers many receptors (TNF, etc.) to be internalized
and activated avoiding cardiomyocyte apoptosis.

Further
studies are in progress to finally decipher the different steps of the
mechanism in order to provide data to design novel efficient drugs able to
reduce the impact of the apoptosis on the injured myocardium.

2) Cardiac
Tissue Engineering

Degenerative
diseases are the main cause of death worldwide and there is a compelling need
for new solutions to treat damaged organs and to address the shortage of donors
and the extensive disability determined by these diseases. In this respect, the
prowess of stem cells to repair tissues hit by degenerative disorders has
sparked off universal interest, as no other medical achievement in the history
of mankind. Nonetheless, the innumerable efforts so far endeavored worldwide
have not yet brought the possibility of repairing most of “solid tissues” (heart,
brain, liver, etc.) and organs by administering stem cells to fruition. A decade
of intensive and highly funded research has neither led to the identification
of the differentiating potential of the diverse stem cell populations nor of
the critical array of factors required to generate a specific cell phenotype.
On the other hand, techniques to characterize stem cells in vitro, and then implant
them and promote their engraftment into damaged organs, as well as protocols to
by-pass the natural regenerative limits of stem cells are still unsafe and
inefficient. In spite of this contingency, some institutions were not dissuaded
from establishing clinical centers to offer ethically questionable ‘‘miraculous’’
treatments to otherwise incurable patients.

LCMC
believes that tissue engineering represents a leap forward in defining
standardized, affordable and efficient treatments for cardiac diseases. For
this reason, LCMC is committed to contribute to improve the knowledge about all
aspects of tissue engineering. This is possible thanks to the multidisciplinary
investigators actively networking with the laboratory.

In
particular, LCMC investigations have dealt with:

(1)   Resident cardiac
progenitor cells (murine and human)

(2)   Bone-marrow derived stem
cells (murine and human)

(3)   Ex-vivo fabrication of
human engineered tissues for cardiac and non-cardiac repair

(4)   Novel biocompatibile
polymers and nanocomposites

(5)   Innovative systems for
stem cell culture and differentiation

In this context, special attention
is paid to investigate how the complexity of the myocardial architecture can be
mimicked and how differently designed scaffolds can drive the fate of stem
cells isolated from the auricles of the patients candidate to be implanted with
the final engineered tissue. Among others, it has been possible to ascertain
that the scaffold stiffness and topology are potent factor in promoting stem
cell differentiation to cardiomyocytes, while cerium dioxide (ceria) plays a
special role in protecting stem cells against the oxidative stress. Novel
concepts in the use of hydrogels are also investigated.

These studies have allowed to
ascertain that the scaffold design is pivotal in activating differentiating
intracellular signaling cascades and that the myocardium is avid of
supernumerary cells when the intramyocardial ecosystem is appropriate. Further
studies are in progress to understand how exploiting these results for potential
clinical applications.