We investigate whether BM-derived rat mesenchymal stem cells(MSCs) can successfully be seeded on a biodegradable polymer(PGCL scaffold) and evaluate the feasibility of this tissue-engineered MSC therapy for myocardial regeneration and functional improvement in a rat model of MI.
For ex vivo studies, DAPI-labeled MSCs(2×106 cells) were seeded on a 5×5mm2-sized PGCL scaffold and cultured for 48 hours and engraftment and survival were evaluated. For in vivo studies, MSC-seeded PGCL graft was implanted on the epicardial myocardium of normal rat heart(n=8) or infarcted heart(n=8) at 1 week after MI. Morphological, immunohistochemical, hemodynamic and functional changes were evaluated at 1, 2 and 4 weeks after graft implantation.
The inoculated MSCs were well attached, seeded and survived in PGCL scaffold when observed by scanning EM. When MSC-seeded PGCL graft was implanted on the epicardium of normal heart or infarcted heart, DAPI-labeled MSCs within the PGCL graft survived up to 4 weeks. MSCs were migrated from PGCL graft into epicardium and myocardium in normal heart group and a few MSCs were penetrated into infarcted tissue and formed more capillaries in infarcted heart group. Those migrated MSCs from scaffold to the heart were positive for the αMHC and cardiac troponin I suggesting myocardial differentiation of MSCs. When MSC-seeded PGCL graft was implanted to infarcted myocardium(n=6), left ventricular end-diastolic dimension was significantly reduced (control 11.1±0.5 mm vs MSC-seeded PGCL graft 8.0±0.8 mm, p<0.0001) and LV end-systolic dimension of graft group (4.9±1.1 mm) was also smaller than that of MI only (9.4±0.4 mm, p<0.0001). Left ventricular fractional shortening (control vs graft; 16.4±3.3 vs 39.5±10.2 %, p<0.001) and LVEDP (control vs graft; 15.8±6.5 vs 5.7±5.6 mmHg, p<0.01) were also improved by the MSC-seeded PGCL graft implantation in the myocardial infarction.
Although this study has the limitation of small number, this new strategy to deliver stem cells seeded on a scaffold could be used as one of modalities for myocardial regeneration and functional improvement in the infarcted heart.
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