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outcomes of ischemic heart disease patients by reducing morbidity and mortality [ 2 ,
3 ]. However, despite their manifold benefits, these agents are incapable of replacing
myocardial tissue that is lost due to ischemic injury. Therefore, there remains a need
for newer forms of therapy, which may potentially reverse the loss of functional
cardiomyocytes and induce effective myocardial reconstitution. Since the turn of
the century, stem cell therapy has emerged as a viable candidate to fill this therapeu-
tic void. By virtue of their reparative capabilities, cell therapy may indeed poten-
tially heal cardiac tissue that was once considered permanently lost.
Because of this unprecedented promise of cardiac repair potentially attainable
with cell therapy, numerous clinical trials with various types of cells have already
been completed and many others are underway. However, and somewhat disap-
pointingly, the efficacy of cell therapy toward inducing infarct repair has remained
controversial. Given the differences in outcomes with regard to cardiac structure
and function, it has been suggested that the results may be influenced by the choice
of imaging techniques. In this chapter, we will provide an overview of cell therapy
and discuss the advantages and disadvantages of imaging modalities that have been
used in cell therapy clinical trials.
9.1 Evolution of Cardiac Cell Therapy
The concept that cells can be utilized to replace or repair injured myocardium
emerged in the 1990s. At that time, it was believed that cardiomyocytes were termi-
nally differentiated cells and incapable of further cell division. In one of the early
preclinical reports, Marelli et al. sought to solve this problem by transplanting skel-
etal muscle satellite cells after myocardial injury induced by application of a cryo-
probe in dogs [ 4 ]. The histological studies showed evidence of cellular retention at
the sites of satellite cell injection in the scar area. In the subsequent years, several
different types of cells were evaluated for their potential of myocardial integration
and repair in different preclinical models of cardiac injury or uninjured hearts [ 5 – 10 ].
Around the same time, in a seminal paper in 1998, Anversa et al. contradicted the
notion that ventricular myocytes are terminally differentiated by demonstrating that
myocytes in adult mammalian hearts were capable of re-entering the cell cycle and
undergoing cell division [ 11 ]. These observations led to great fervor in the scientific
community, and fast-tracked cell-based therapy into clinical application [ 12 – 15 ].
The first use of cell therapy in humans dates back to a study reported in 2001,
wherein Menasche et al. implanted autologous skeletal muscle myoblasts into the
myocardial scar during coronary artery bypass surgery in a patient with ischemic
heart failure [ 12 ]. At follow-up after 5 months, the investigators noticed evidence of
contraction and viability in the grafted scar by echocardiography and PET. The field
of cell therapy for ischemic heart disease has since greatly expanded to include
numerous different types of cells in small clinical trials with each enrolling a small
number of patients [ 13 , 14 , 16 – 19 ]. The designs of these trials have varied
significantly from each other with regard to cell type, cell processing, number of
A. Samanta et al.