Abstract
Background:
Mesenchymal stem cells (MSCs) improve ventricular function post MI
Hypothesis:
Transendocardial stem cell injections (TESI) reverse remodeling in a swine model of chronic ischemic cardiomyopathy (CIC).
Methods:
Gottingen swine (n=12), underwent a closed-chest, LAD occlusion-reperfusion model to create chronic ischemic cardiomyopathy. Three months post-MI, transendocardial injections of allogeneic MSCs (n=6) or sham injection (control group, n=6) were administered to the infarct and border zones. Cardiac MRI and pressure volume loops were obtained at baseline, during injection, and 6 months post injection. The three dimensional sphericity index (SI) was determined using the formula, SI= (π x LVLA3)/6, where LVLA is the left ventricle long axis length as measured in a 4-chamber long axis cardiac MRI end diastolic frame perpendicular to the line from the annulus of the mitral valve to the apex.
Results:
The sphericity index increased in both groups 3 months after MI, from 0.268 ± 0.054 to 0.348 ± 0.050 in the sham injection group and 0.277 ± 0.051 to 0.380 ± 0.059 in the TESI group. In the sham injection group, SI remained stable 9 months post sham injections indicative of irreversible remodeling post MI. In contrast, the injection group SI continued to decrease from 0.380 ± 0.059 to 0.346 ± 0.064 and 0.280 ± 0.50 at 3 and 6 months post TESI, respectively.
Conclusions:
Measurements of SI show that transendocardial stem cell injections of allogeneic MSCs demonstrate the potential to reverse left ventricular remodeling in CIC patients to geometric configurations comparable to their pre-MI shapes.