Bone marrow-derived autologous human mesenchymal stem cells (MSCs) are one of the most promising cell sources for
cell therapy to treat
heart failure. The cell sheet technique has allowed
transplantation of a large number of cells and enhanced the efficacy of
cell therapy. We hypothesized that the
transplantation of MSC sheets may be a feasible, safe, and effective treatment for ischemic
cardiomyopathy (ICM).
METHODS AND RESULTS: Human MSCs acquired from bone marrow were positive for CD73, CD90, and CD105 and negative for CD11b and CD45 by flow cytometry. Ten MSC sheets were created from a total cell number of 1×10(8) MSCs using temperature-responsive culture dishes. These were successfully transplanted over the
infarct myocardium of porcine ICM models induced by placing an
ameroid constrictor on the left anterior descending coronary artery without any procedural-related complications (MSC group=6: sheet
transplantation;
sham group=6, oral intake of
tacrolimus in both groups).
Premature ventricular contractions were rarely detected by Holter electrocardiogram (ECG) in the MSC group in the first week after
transplantation. On echocardiography, the cardiac performance of the MSC group was significantly better than that of the
sham group at 8 weeks after
transplantation. On histological examination 8 weeks after
transplantation, left ventricular (LV) remodeling was significantly attenuated compared with the
sham group (cardiomyocyte size and interstitial
fibrosis were measured). Immunohistochemistry of the
von Willebrand factor showed that the vascular density in the
infarct border area was significantly greater in the MSC group than the
sham group. Expression of angiogenesis-related factors in the
infarct border area of the MSC group was significantly greater than that of the
sham group, as measured by real-time polymerase chain reaction.
CONCLUSIONS: Bone marrow-derived MSC sheets improved cardiac function and attenuated LV remodeling in ICM without major complications, indicating that this strategy would be applicable in clinical settings.