107Studies by Marban’s group have cultured human endomyocardial biopsies-
derived CSCs into CDCs and transplanted these into acute myocardial infarcts in
immunodeficient mice and pig model of heart failure after myocardial infarction
[ 16 , 32 ]. The results depict that the transplanted cells engraft and migrate into the
infarct zone and lead to improvement in cardiac functions such as LVEF and attenu-
ation of ventricular remodeling. In another study by Suzuki G, it has been demon-
strated that slow infusion of CDCs into the three major coronary arteries (total dose:
30 million CDCs) in swine with hibernating myocardium improved regional func-
tion in ischemic LAD as well as in the normal right coronary artery regions (68–
107%, P < 0.05) and ejection fraction [ 33 ].
In a study by Lee et al., the investigators have compared the effects of CDCs and
their precursor cells, cardiospheres, which are heterogenous groups of cells that
contain not only adult CSCs, capable of long-term self-renewal and cardiomyocyte
differentiation, but also vascular cells and differentiated progenitor cells in a swine
MI model [ 32 ]. The study has reported that the effects on infarct reduction and pres-
ervation of EF is similar in both CDCs and cardiospheres, however hemodynamics,
regional function and preservation of LV chamber remodeling are improved in
animals receiving cardiospheres, suggesting the benefits of heterogeneous cell
therapy.
7.5 Clinical Trials with CSCs
Although there are many success stories of CSCs in experimental models, many
challenges still await their therapeutic use in the clinical arena. Encouraging results
from the animal studies formed the basis for the first clinical trial of c-kit+ CSCs,
Cardiac Stem Cell Infusion in Patients with Ischemic Cardiomyopathy (SCIPIO).
SCIPIO involved 23 patients who had experienced MI in the past and exhibited an
EF of under 40%. One million of autologous cKit+ and lineage negative CSCs were
isolated with magnetic beads from cultures of right atrial appendage tissue and
administered via intracoronary infusion 1 month after coronary artery bypass graft-
ing (CABG). Twelve months after the treatment, infarct size was decreased by
30.2%, regional wall thickening was increased by 18% and left ventricular EF was
increased by 8.2%. The benefits of treatment continued to increase and left ventricu-
lar EF was increased by 12% after 2 years [ 34 ].
Another trial, named CADUCEUS, which is CArdiosphere-Derived aUtologous
stem CElls to reverse ventricUlar dySfunction trial evaluated the safety and efficacy
of intracoronary autologous CDCs in 17 patients with left ventricular dysfunction
after MI. Six patients were included as control patients who were not given CDC
treatment. The cardiospheres were expanded ~36 days in culture from right ven-
tricular endomyocardial biopsies taken 2–4 weeks after acute myocardial infarction
and injected into the previously stented coronary artery between 6–12 weeks after
the heart attack. Despite the lack of improvement in left ventricular EF or patient
reported outcomes, there were reductions of scar mass in CDC-treated patients by
7 The Emerging Role of Cardiac Stem Cells in Cardiac Regeneration