113LVEF at 4 months and reduction in combined clinical end points of death, recurrence
of AMI, and any revascularization procedure at 1 year. However, other groups from
Belgium and Norway, have been unable to detect a difference in outcome between
bone marrow cell treated group and controls in AMI setting [ 70 ]. Different cell
isolation protocols as well as dosage, degree of cell viability and function prior to
delivery may contribute to the heterogeneous clinical results in randomized trials. In
the (transplantation of progenitor cells and recovery of LV function in patients with
chronic ischemic heart disease) TOPCARE-CHD trial, the absolute change in LVEF
at 3 months, was significantly greater among patients receiving the bone marrow
cells than among those receiving circulating progenitor cells [ 71 ]. Cochrane Heart
Group have studied 33 clinical trials (1765 patients) for effectiveness of BM-cells
for cardiac regeneration following acute MI. They have concluded that while no
significant improvement was observed in the mortality and morbidity of the patients
who received BM-cells, a significant and sustained improvement (in LVEF was
there during 12–61 months follow-up period [ 72 ]. In another meta- analysis, the
same group has reported that, in addition to the improvement in LVEF, BM-cells are
also able to improve the morbidity and mortality in patients with chronic heart dis-
ease and congestive heart failure [ 73 ]. Although, much advancement has been made
in the area of BM-stem cells therapeutics and cardiac regeneration, which and how
specific population of cells from the BM actually contributes to cardiac repair is not
yet conspicuous. Whatever it may be, it is definite that the BM-heart axis plays a
pivotal role in heart regeneration after injury.
Exciting new advances in cardiomyocyte regeneration are also being made in
human embryonic stem cell research. Studies have shown that hESCs can reproduc-
ibly differentiate in culture into embryoid bodies and the cells have structural and
functional properties of early stage cardiomyocytes [ 74 , 75 ]. In experimental stud-
ies, the transplantation of mESC-derived cardiomyocytes into the injured hearts of
immunocompatible mice has resulted in the formation of stable intracardiac grafts
[ 76 ]. In 2004, Kehat et al. reported human cardiomyocyte transplantation into the
uninjured swine myocardium [ 77 ]. The transplantation of ESC-derived cardiomyo-
cytes into normal and injured heart in animals has been shown to improve the global
myocardial function, although for a short period of time. Efforts are now directed at
identifying defined factors to enhance the differentiation of cardiomyocytes from
hESC [ 78 ]. Recently Chong et al have succeeded in generating cardiomyocytes
from ESCs on a large scale. These ESC-CMs are able to successfully engraft and
repair the injured myocardium in a primate model of myocardial infarction [ 79 ].
Despite the evidence of ESCs efficacy in larger animal models, their clinical use has
been hampered due to many reasons, including their genetic instability, risk of
arrhythmias, potential tumorigenic and immunogenic properties, little improvement
in cardiac functions and finally ethical considerations related to the origin of these
cells. Besides these cell types, induced pluripotent cells (iPS) have also been con-
verted to cardiac progenitors in vitro and upon intramyocardial delivery into adult
infarcted animal hearts, these cardiogenic iPS progeny have shown proper engrafte-
ment without disrupting the host tissues [ 80 – 82 ]. Importantly, iPS-based transplan-
tation have shown to restore post-ischemic cardiac performance with evidence of
7 The Emerging Role of Cardiac Stem Cells in Cardiac Regeneration