Autologous Mesenchymal Stem Cells Produce Concordant Improvements in Regional Function, Tissue Perfusion, and Fibrotic Burden When Administered to Patients Undergoing Coronary Artery Bypass Grafting
RATIONALE:
Although accumulating data support
the efficacy of intramyocardial cell-based therapy to improve left
ventricular (LV) function in patients with chronic ischemic
cardiomyopathy undergoing CABG, the underlying mechanism and impact of
cell injection site remain controversial. Mesenchymal stem cells (MSCs)
improve LV structure and function through several effects including
reducing fibrosis, neoangiogenesis, and neomyogenesis.
OBJECTIVE:
To test the hypothesis that the impact on cardiac
structure and function after intramyocardial injections of autologous
MSCs results from a concordance of prorecovery phenotypic effects.
METHODS AND RESULTS:
Six
patients were injected with autologous MSCs into akinetic/hypokinetic
myocardial territories not receiving bypass graft for clinical reasons.
MRI was used to measure scar, perfusion,
wall thickness, and contractility at baseline, at 3, 6, and 18 months
and to compare structural and functional recovery in regions that
received MSC injections alone, revascularization alone, or neither. A
composite score of MRI variables was used to assess concordance of
antifibrotic effects, perfusion,
and contraction at different regions. After 18 months, subjects
receiving MSCs exhibited increased LV ejection fraction (+9.4±1.7%,
P=0.0002) and decreased scar mass (-47.5±8.1%; P<0.0001) compared
with baseline. MSC-injected segments had concordant reduction in scar
size, perfusion,
and contractile improvement (concordant score: 2.93±0.07), whereas
revascularized (0.5±0.21) and nontreated segments (-0.07±0.34)
demonstrated nonconcordant changes (P<0.0001 versus injected
segments).
CONCLUSIONS:
Intramyocardial injection of
autologous MSCs into akinetic yet nonrevascularized segments produces
comprehensive regional functional restitution, which in turn drives
improvement in global LV function. These findings, although inconclusive
because of lack of placebo group, have important therapeutic and
mechanistic hypothesis-generating implications.
CLINICAL TRIAL REGISTRATION URL:
http://clinicaltrials.gov/show/NCT00587990. Unique identifier: NCT00587990.
