135cells, route and timing of cell injection, recipient patient population, duration of
follow- up, and mode of cardiac imaging. Although effective repair of infarcted and/
or cardiomyopathic myocardium has been reported with several different cell types,
BMCs have been utilized most widely for cardiac repair in patients with ischemic
heart disease.
9.2 Bone Marrow Cell Therapy for Ischemic Heart Disease
The early success with BMCs for heart repair in animal models coupled with the
ease of acquisition of these cells led to rapid translation of BMC therapy in humans.
In early clinical studies, Hamano et al. injected autologous BMCs into the scar tis-
sue of five patients with ischemic heart disease during coronary artery bypass graft
surgery and followed them for a year [ 20 ]. They reported an improvement in myo-
cardial perfusion by cardiac scintigraphy in three of the five BMC-treated patients.
Strauer et al. injected autologous BMCs into the infarct-related artery after PCI in
patients with acute MI and compared outcomes with a control group [ 13 ]. They
reported reduced infarct size and improved myocardial contractility and perfusion
in BMC-treated patients. Importantly, global LVEF and left ventricular end- diastolic
volume (LVEDV) did not change significantly.
The BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST)
trial was the first randomized controlled trial (RCT) of BMC therapy for myocardial
repair [ 21 ]. In this study, 60 patients were randomized to receive either BMC therapy
or standard of care following percutaneous coronary intervention (PCI) for acute
ST-segment elevation MI. After 6 months of follow-up, cardiac MRI showed increase
in global LVEF by 0.7 percentage points in the control group and 6.7 percentage
points in the cell therapy group, indicating that BMC therapy was associated with a
significant improvement in cardiac function. However, after 18 months of follow-up,
LVEF improved by 3.1 percentage points in the control group and 5.9 percentage
points in the BMC group, but there was no significant difference between these
groups [ 22 ]. These observations led to the notion that although BMC therapy signifi-
cantly improves cardiac function during early follow-up, these advantages are even-
tually lost over longer term. The 18-month follow-up data from BOOST, however,
did show an improvement in diastolic function in BMC-injected patients [ 23 ]; and
the 5-year follow-up data showed significant improvement in cardiac function by
MRI in BMC-treated patients with greater infarct transmurality [ 24 ].
With the rapid increase in the number of BMC trials for cardiac repair, the differ-
ences in outcomes with such therapy also became apparent. For example, the results
from two RCTs, Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in
Acute Myocardial Infarction (REPAIR-AMI) and Autologous Stem-Cell
Transplantation in Acute Myocardial Infarction (ASTAMI) trials, both of which
used similar BMC populations in patients with acute MI, were remarkably different.
REPAIR-AMI randomized 204 patients to receive either intracoronary injection of
autologous BMCs or standard therapy at 3–7 days after PCI for acute MI. After 4
9 Bone Marrow Cell Therapy for Ischemic Heart Disease...