121must be controlled to allow for the regression of tissue amyloid deposits.
Hematopoietic cell transplantation permits delivery of myeloablative doses of mel-
phalan and is an effective therapy for eligible patients to achieve hematologic
response. However, whether such elimination of the plasma cell clone can lead to
reversal of organ damage, such as cardiac amyloidosis, is not clear. The authors
examined the possibility that autologous BMT might improve cardiac function in
patients with MM and cardiac amyloidosis using cardiac MRI as the diagnostic tool.
Our study showed significant improvement in LV systolic function in each of the
patients with low ejection fraction following BMT. Interestingly, cardiac MRI
showed no change in delayed enhancement pattern in these patients. This cardiac
MRI pattern suggests that the improvement in LV systolic function was not due to
resolution of amyloid infiltrate, but most likely it was related to bone marrow stem
cells homing into the myocardium and differentiating into new cardiomyocytes that
would participate in cardiac contractility. Some previous studies have indeed shown
that homing of stem cells in the ischemic myocardium improves LV function and
outcome [ 20 , 21 ]. Experimental studies suggest that transfer of stem cells and pro-
genitor cells can have a favorable impact on perfusion and contractile performance
of the failing heart. Preliminary efficacy data indicate that stem cells have the poten-
tial to enhance myocardial perfusion and/or contractile performance in patients with
acute myocardial infarction, advanced coronary artery disease, and chronic heart
failure [ 20 ]. The intracoronary delivery of unselected bone marrow cells has recently
been shown to enhance LV EF recovery in patients after acute myocardial infarction
[ 21 ]. Our study suggests that some degree of heart failure may be a pre-requisite for
improvement in cardiac function. The failing heart potentially creates a more com-
patible nidus for the homing of progenitor cells with release of many inflammatory
markers and chemokines. The failing heart is also likely more apt for signaling and
recruitment of bone marrow stromal cells to the myocardium following
BMT. Notably, we were not able to show a direct correlation of a number of inflam-
matory signals such as CD-19, IL-6 and CD-4 and hs-CRP and improvement in LV
function. There can be several reasons for lack of this correlation: these markers
may not reflect chemokines and cytokines that induce mobilization and homing of
progenitor cells; or measurement at a single time point before BMT may not cor-
relate with improvement several months following BMT. Most likely, it is a combi-
nation of several known and unknown signals that induces mobilization, homing
and transformation of stem cells into cardiomyocytes.
Similar to our observations, several other individual studies have shown improve-
ment in cardiac function following stem cell therapy [ 18 , 20 – 22 ]. However, con-
flicting results have also been noted in several multicenter phase 3 studies employing
BMMC injection with no significant changes in ejection fraction [ 23 , 24 ]. The vari-
able results are likely due to the fact that successful regeneration in the heart requires
the injected cell to be delivered to the correct zone of the myocardium, survive in
the host microenvironment, exert beneficial paracrine effects, differentiate, and inte-
grate with the host myocardium. Thus there are multiple variable that affect homing
of adequate number of cells in the appropriate site and their cellular transformation
into cardiomyoctes. The rapid washout of the stem cells from the myocardium is
8 Cardiac Imaging and Stem Cell Transplantation