Abstract 17831: Transplantation of Human Pericyte Progenitor Cells Enhances Reparative Arteriogenesis and Attenuates Ventricular Dysfunction in a Mouse Model of Myocardial Infarction
Objective: Clinical evidence indicates that transplantation of heterogeneous cell populations helps the healing of infarcted heart by various ways including paracrine promotion of angiogenesis. To selectively address vascular needs by specialized cytotherapy, we verified the potential of clonogenic human pericyte progenitors (HPP) in a model of myocardial infarction (MI).
Methods: HPP were enriched from saphenous vein leftovers of patients undergoing CABG. Immunodeficient CD1/Foxn-1nu/nu mice, submitted to occlusion of left anterior descending coronary artery, were randomized to receive 1X106 HPP or vehicle (n=15 per group) at 3 sites of the MI border zone. Functional recovery was monitored by echocardiography before and 14d post-MI, followed by intraventricular pressure measurement and collection of hearts for histology. Samples were also collected at 5d post-MI to verify the engraftment of HPP using whole mount immunohistochemistry (IHC).
Results: Transplantation of HPP increased anterior wall thickness (P<0.001) and attenuated left ventricular (LV) dysfunction (EF: 26±3 vs 18±3% and CO: 16±1 vs 12±2ml/min; P<0.01 vs vehicle for both comparisons). HPP markedly improved pressure indices (LVEDP: 7.8±0.9 vs 10.0±0.8 mmHg, dP/dtmax: 4880±115 vs 4370±199 and dP/dtmin: 3935±219 vs 3434±156 mmHg/sec, P<0.05 for all comparisons). HPP reduced myocardial scar dimensions (Azan-Mallory staining, 32±2 vs 38±2% of LV wall, P<0.05). Moreover, HPP increased the density of αSMA-positive arterioles in the border-zone (58±6 vs 43±2 per mm2, P<0.01) and produced a mild increase in capillary density (5540±218 vs 5225±114 per mm2, P=0.08). Finally, whole mount IHC demonstrated the alignment of transplanted HPP, some positive for proliferating cell nuclear antigen (1.4±0.4%), along vessels sprouting toward the infarct area (Figure).
Conclusions: Taken together, HPP therapy of MI benefits cardiac function through implementation of neovascularization.
- © 2010 by American Heart Association, Inc.